Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo

Los virus oncolíticos son virus naturales o genéticamente modificados que tienen la capacidad de infectar las células cancerígenas, replicarse dentro de ellas causando su destrucción y de esta manera estimular la respuesta antitumoral del huésped. Por otra parte el cáncer de mama es de gran importan...

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Autores:
Buitrago Mejía, Lorena
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2018
Institución:
Colegio Mayor de Cundinamarca
Repositorio:
Repositorio Colegio Mayor de Cundinamarca
Idioma:
spa
OAI Identifier:
oai:repositorio.unicolmayor.edu.co:unicolmayor/4781
Acceso en línea:
https://repositorio.unicolmayor.edu.co/handle/unicolmayor/4781
Palabra clave:
Virus naturales
Células
Cáncer
Cáncer
Respuesta inmune
Virus oncolíticos
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closedAccess
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Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2018
id UCOLMAYOR2_8bd67f8469457ed0dba18c140c38251d
oai_identifier_str oai:repositorio.unicolmayor.edu.co:unicolmayor/4781
network_acronym_str UCOLMAYOR2
network_name_str Repositorio Colegio Mayor de Cundinamarca
repository_id_str
dc.title.spa.fl_str_mv Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
title Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
spellingShingle Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
Virus naturales
Células
Cáncer
Cáncer
Respuesta inmune
Virus oncolíticos
title_short Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
title_full Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
title_fullStr Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
title_full_unstemmed Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
title_sort Revisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivo
dc.creator.fl_str_mv Buitrago Mejía, Lorena
dc.contributor.advisor.none.fl_str_mv Hernández, Edith del Carmen
Rodríguez Panduro, Mauricio Humberto
dc.contributor.author.none.fl_str_mv Buitrago Mejía, Lorena
dc.subject.lemb.none.fl_str_mv Virus naturales
Células
Cáncer
topic Virus naturales
Células
Cáncer
Cáncer
Respuesta inmune
Virus oncolíticos
dc.subject.proposal.spa.fl_str_mv Cáncer
Respuesta inmune
Virus oncolíticos
description Los virus oncolíticos son virus naturales o genéticamente modificados que tienen la capacidad de infectar las células cancerígenas, replicarse dentro de ellas causando su destrucción y de esta manera estimular la respuesta antitumoral del huésped. Por otra parte el cáncer de mama es de gran importancia en salud pública con un número de casos que crece a través del tiempo. Dentro de su clasificación se encuentra el cáncer de mama HER2 positivo que es de mal pronóstico, agresivo y de alto grado histológico alto, que incrementa con el diagnóstico tardío. En esta revisión bibliográfica se recopiló información significativa sobre los virus oncolíticos y su posible empleabilidad en el tratamiento de cáncer de mama, descripción de su potencial, y los diferentes mecanismos de acción que los hacen agentes biológicos excelentes en terapias anti cáncer. Los resultados arrojan que la mayoría de investigaciones con virus oncolíticos se realizan en EEUU, y los virus más empleados para ensayos cáncer de mama son el virus del herpes simplex con un 31% y el adenovirus con un 13%; estos virus modificados permiten activar el sistema inmune, aumentar la selectividad hacia la célula tumoral, promover la creación de anticuerpos contra un blanco especifico, ser útiles como marcadores de seguimiento, entre otros. Con esta revisión de literatura se espera motivar a los investigadores a incrementar sus ensayos no solo con otros virus oncolíticos sino también con diferentes blancos terapéuticos en el cáncer de mama que permitan ampliar las opciones terapéuticas en los pacientes, en especial el cáncer de mama HER2 positivo. Que si bien, de acuerdo a esta revisión para cáncer de mama HER2 positivo no hay una muestra representativa de experimentos que ayuden a concluir si es o no factible una alternativa terapéutica con virus oncolíticos.
publishDate 2018
dc.date.issued.none.fl_str_mv 2018-11
dc.date.accessioned.none.fl_str_mv 2022-03-07T20:25:15Z
dc.date.available.none.fl_str_mv 2022-03-07T20:25:15Z
dc.type.spa.fl_str_mv Trabajo de grado - Pregrado
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content.spa.fl_str_mv Text
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/TP
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_7a1f
status_str publishedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unicolmayor.edu.co/handle/unicolmayor/4781
dc.identifier.barcode.none.fl_str_mv 58661
url https://repositorio.unicolmayor.edu.co/handle/unicolmayor/4781
identifier_str_mv 58661
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv MINSALUD. Cáncer de mama, una enfermedad en ascenso en Colombia [Internet]. 2014 [cited 2018 Mar 20]. Available from: https://www.minsalud.gov.co/Paginas/-Cancer-de-mama,-unaenfermedad-en-ascenso-en-Colombia.aspx
Viviana Y, Márquez A, Balcázar IB, Aristizábal FA. Tratamiento de cáncer de seno y farmacogenética Treatment of breast cancer and pharmacogenetics. Rev Colomb Biotecnol [Internet]. 2016 [cited 2018 Feb 20]; Available from: http://www.scielo.org.co/pdf/biote/v18n1/v18n1a14.pdf
McCafferty MPJ, Healy NA, Kerin MJ. Breast cancer subtypes and molecular biomarkers. Diagnostic Histopathol [Internet]. 2009 Oct 1 [cited 2017 Oct 26];15(10):485–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1756231709001455
D MK, S A-D. Efectos del Trastuzumab como Terapia Coadyuvante para Pacientes con Cáncer de Mama Her2-Positivo: Una Revisión Sistemática. Arch Med [Internet]. 2017 Aug 5 [cited 2017 Oct 27];13(3). Available from: http://www.archivosdemedicina.com/medicina-de-familia/efectos-deltrastuzumab-como-terapia-coadyuvante-para-pacientes-con-caacutencerde-mama-her2positivo-una-revisioacuten-sistemaacut.php?aid=20055
Garnock-Jones KP, Keating GM, Scott LJ. Trastuzumab. Drugs [Internet]. 2010 Jan [cited 2017 Oct 27];70(2):215–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20108993
Arrese I, González P, Miranda P, Perez-Nuñez P, Pascual B, Lobato RD. Tratamiento de los gliomas mediante virus oncolíticos: revisión de la literatura. Neurocirugia. 2005;16:158–68.
Rodríguez L. CAGF. LA PROTEÍNA VIRAL VP6 DE ROTAVIRUS COINMUNOPRECIPITA CON HSC70 EN CÉLULAS MA104. 2006;
Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther [Internet]. 2007;15(4):651–9. Available from: http://dx.doi.org/10.1038/sj.mt.6300108
jaime R. merchan barros, jun j. madera merchan sheila p. auz ramirez. viroterapia mediante virus oncoliticos en tumores sólidos [Internet]. 2011. Available from: http://medpre.med.ec/secciones/medicina/1 revista/Viroterapia mediante virus oncoliticos en tumores solidos.pdf
Ramos Guette PL. Características clínicas y mortalidad en pacientes con cáncer de mama avanzado (estados iiia iiib iiic) en colombia, clínica oncocare, 2003–2012. Rev Colomb Cancerol [Internet]. 2013 Dec 1 [cited 2018 Mar 8];17(4):180–1. Available from: https://www.sciencedirect.com/science/article/pii/S0123901513702002
Rodríguez JA, Martínez LM, Cruz N, Cómbita AL. Terapia génica para el tratamiento del cáncer. Rev Colomb Cancerol [Internet]. 2014;18(1):27– 40. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0123901514702227
Cho M. Bioinformatics research on the specificity and safety of oncolytic viruses. 2015 [cited 2017 Oct 13]; Available from: http://sspace.snu.ac.kr/handle/10371/128348
Dutilh BE, Reyes A, Hall RJ, Whiteson KL. Editorial: Virus Discovery by Metagenomics: The (Im)possibilities. Front Microbiol [Internet]. 2017 Sep 8 [cited 2017 Sep 26];8:1710. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28943867
Lawler SE, Speranza M-C, Cho C-F, Chiocca EA, RL M, BD L, et al. Oncolytic Viruses in Cancer Treatment. JAMA Oncol [Internet]. 2016;2(12):938–50. Available from: http://oncology.jamanetwork.com/article.aspx?doi=10.1001/jamaoncol.2 016.2064
Suryawanshi YR, Zhang T, Essani K. Oncolytic viruses: emerging options for the treatment of breast cancer. Med Oncol [Internet]. 2017 Mar 9 [cited 2018 Mar 15];34(3):43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28185165
Miest TS, Cattaneo R. New viruses for cancer therapy: meeting clinical needs. Nat Rev Microbiol [Internet]. 2014 Jan 2 [cited 2018 Aug 13];12(1):23–34. Available from: http://www.nature.com/articles/nrmicro3140
Release FDAN, Release FI. FDA approves first of its kind product for the treatment of melanoma. 2016;1–4. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm54 8278.htm
Bramante S, Koski A, Liikanen I, Vassilev L, Oksanen M, Siurala M, et al. Oncolytic virotherapy for treatment of breast cancer, including triplenegative breast cancer. Oncoimmunology [Internet]. 2016 Feb [cited 2018 Aug 20];5(2):e1078057. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27057453
Talimogene laherparepvec for melanoma. Aust Prescr [Internet]. 2017 Feb [cited 2018 Mar 15];40(1):38–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28246438
Hummel JL, Safroneeva E, Mossman KL. The role of ICP0-Null HSV-1 and interferon signaling defects in the effective treatment of breast adenocarcinoma. Mol Ther [Internet]. 2005 Dec [cited 2018 Aug 22];12(6):1101–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16140040
Sahin TT, Kasuya H, Nomura N, Shikano T, Yamamura K, Gewen T, et al. Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer. Cancer Gene Ther [Internet]. 2012 Apr 23 [cited 2018 Mar 16];19(4):229–37. Available from: http://www.nature.com/articles/cgt201180
Thomas DL, Fraser NW. HSV-1 therapy of primary tumors reduces the number of metastases in an immune-competent model of metastatic breast cancer. Mol Ther [Internet]. 2003 Oct 1 [cited 2018 Jul 29];8(4):543–51. Available from: https://www.sciencedirect.com/science/article/pii/S1525001603002363
Cody JJ, Markert JM, Hurst DR. Histone Deacetylase Inhibitors Improve the Replication of Oncolytic Herpes Simplex Virus in Breast Cancer Cells. PLoS One [Internet]. 2014 [cited 2018 Jul 29];9(3):e92919. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092919
Chen X, Han J, Chu J, Zhang L, Zhang J, Chen C, et al. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases. Oncotarget [Internet]. 2016 May 10 [cited 2018 Jul 29];7(19):27764–77. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27050072
Walker JD, Sehgal I, Kousoulas KG. Oncolytic herpes simplex virus 1 encoding 15-prostaglandin dehydrogenase mitigates immune suppression and reduces ectopic primary and metastatic breast cancer in mice. J Virol [Internet]. 2011 Jul [cited 2018 Aug 22];85(14):7363–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21543507
Fasullo M, Burch A, Britton A. Hypoxia enhances the replication of oncolytic herpes simplex virus in p53- breast cancer cells. Cell Cycle [Internet]. 2009 Jul 15 [cited 2018 Jul 29];8(14):2194–7. Available from: http://www.tandfonline.com/doi/abs/10.4161/cc.8.14.8934
Pourchet A, Fuhrmann SR, Pilones KA, Demaria S, Frey AB, Mulvey M, et al. CD8+ T-cell Immune Evasion Enables Oncolytic Virus Immunotherapy. EBioMedicine [Internet]. 2016 Mar 1 [cited 2018 Aug 20];5:59–67. Available from: https://www.sciencedirect.com/science/article/pii/S2352396416300184
Tan G, Kasuya H, Sahin TT, Yamamura K, Wu Z, Koide Y, et al. Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft. Int J Cancer [Internet]. 2015 Apr 1 [cited 2018 Aug 20];136(7):1718–30. Available from: http://doi.wiley.com/10.1002/ijc.29163
Chiocca EA. Oncolytic viruses. Invest New Drugs [Internet]. 2002;17(4):375–86. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12459732
Hirvinen M, Rajecki M, Kapanen M, Parviainen S, Rouvinen-Lagerström N, Diaconu I, et al. Immunological Effects of a Tumor Necrosis Factor Alpha– Armed Oncolytic Adenovirus. Hum Gene Ther [Internet]. 2015 Mar 4 [cited 2018 Aug 20];26(3):134–44. Available from: http://www.liebertpub.com/doi/10.1089/hum.2014.069
1Jiang H, Rivera-Molina Y, Gomez-Manzano C, Clise-Dwyer K, Bover L, Vence LM, et al. Therapeutics, Targets, and Chemical Biology Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination. Cancer Res [Internet]. 2017 [cited 2018 Aug 20];77(14). Available from: http://cancerres.aacrjournals.org/
Hock K, Laengle J, Kuznetsova I, Egorov A, Hegedus B, Dome B, et al. Oncolytic influenza A virus expressing interleukin-15 decreases tumor growth in vivo. Surgery [Internet]. 2017 Mar 1 [cited 2018 Jul 29];161(3):735–46. Available from: https://www.sciencedirect.com/science/article/pii/S0039606016304809
Stoff-Khalili MA, Rivera AA, Mathis JM, Banerjee NS, Moon AS, Hess A, et al. Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma. Breast Cancer Res Treat [Internet]. 2007 Aug 31 [cited 2018 Jul 29];105(2):157–67. Available from: http://link.springer.com/10.1007/s10549-006-9449-8
Bazan-Peregrino M, Carlisle RC, Hernandez-Alcoceba R, Iggo R, Homicsko K, Fisher KD, et al. Comparison of Molecular Strategies for Breast Cancer Virotherapy Using Oncolytic Adenovirus. https://home.liebertpub.com/hum [Internet]. 2008 Sep 16 [cited 2018 Jul 29]; Available from: https://www.liebertpub.com/doi/abs/10.1089/hum.2008.047
Gomes EM, Rodrigues MS, Phadke AP, Butcher LD, Starling C, Chen S, et al. Antitumor Activity of an Oncolytic Adenoviral-CD40 Ligand (CD154) Transgene Construct in Human Breast Cancer Cells. 2009 [cited 2018 Jul 29]; Available from: www.aacrjournals.org
Gentschev I, Stritzker J, Hofmann E, Weibel S, Yu YA, Chen N, et al. Use of an oncolytic vaccinia virus for the treatment of canine breast cancer in nude mice: preclinical development of a therapeutic agent. Cancer Gene Ther [Internet]. 2009 Apr 24 [cited 2018 Jul 29];16(4):320–8. Available from: http://www.nature.com/articles/cgt200887
Yoo SY, Bang SY, Jeong S-N, Kang DH, Heo J. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer. Oncotarget [Internet]. 2016 Mar 29 [cited 2018 Aug 20];7(13):16479–89. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26918725
Gholami S, Marano A, Chen NG, Aguilar RJ, Frentzen A, Chen C-H, et al. A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. Breast Cancer Res Treat [Internet]. 2014 Dec 13 [cited 2018 Aug 20];148(3):489–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25391896
Sugiyama T, Yoneda M, Kuraishi T, Hattori S, Inoue Y, Sato H, et al. Measles virus selectively blind to signaling lymphocyte activation molecule as a novel oncolytic virus for breast cancer treatment. Gene Ther [Internet]. 2013 Mar 21 [cited 2018 Jul 29];20(3):338–47. Available from: http://www.nature.com/articles/gt201244
Iankov ID, Msaouel P, Allen C, Federspiel MJ, Bulur PA, Dietz AB, et al. Demonstration of anti-tumor activity of oncolytic measles virus strains in a malignant pleural effusion breast cancer model. Breast Cancer Res Treat [Internet]. 2010 Aug 6 [cited 2018 Jul 29];122(3):745–54. Available from: http://link.springer.com/10.1007/s10549-009-0602-z
McDonald CJ, Erlichman C, Ingle JN, Rosales GA, Allen C, Greiner SM, et al. A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer. Breast Cancer Res Treat [Internet]. 2006 Sep 27 [cited 2018 Jul 29];99(2):177–84. Available from: http://link.springer.com/10.1007/s10549-006-9200-5
Asada T. Treatment of human cancer with mumps virus. Cancer [Internet]. 1974 Dec [cited 2018 Aug 7];34(6):1907–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4611607
Ammayappan A, Russell SJ, Federspiel MJ. Recombinant mumps virus as a cancer therapeutic agent. Mol Ther - Oncolytics [Internet]. 2016 Jan 1 [cited 2018 Jul 29];3. Available from: https://www.sciencedirect.com/science/article/pii/S2372770517300128
Le Boeuf F, Gebremeskel S, McMullen N, He H, Greenshields AL, Hoskin DW, et al. Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models. Mol Ther - Oncolytics [Internet]. 2017 Sep 15 [cited 2018 Jul 29];6:80–9. Available from: https://www.sciencedirect.com/science/article/pii/S237277051730030X
Olagnier D, Lababidi RR, Hadj SB, Sze A, Liu Y, Naidu SD, et al. Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity. Mol Ther [Internet]. 2017 Aug 2 [cited 2018 Aug 20];25(8):1900–16. Available from: https://www.sciencedirect.com/science/article/pii/S152500161730206X
Bourgeois-Daigneault M-C, Roy DG, Falls T, Twumasi-Boateng K, StGermain LE, Marguerie M, et al. Oncolytic vesicular stomatitis virus expressing interferon-σ has enhanced therapeutic activity. Mol Ther - Oncolytics [Internet]. 2016 Jan 1 [cited 2018 Aug 20];3. Available from: https://www.sciencedirect.com/science/article/pii/S237277051630033X
Platonov ME, Borovjagin A V., Kaverina N, Xiao T, Kadagidze Z, Lesniak M, et al. KISS1 tumor suppressor restricts angiogenesis of breast cancer brain metastases and sensitizes them to oncolytic virotherapy in vitro. Cancer Lett [Internet]. 2018 Mar 28 [cited 2018 Jul 29];417:75–88. Available from: https://www.sciencedirect.com/science/article/pii/S0304383517307966
Sakhawat A, Liu Y, Ma L, Muhammad T, Wang S, Zhang L, et al. Upregulation of Coxsackie Adenovirus Receptor Sensitizes Cisplatin-Resistant Lung Cancer Cells to CRAd-Induced Inhibition. J Cancer [Internet]. 2017 [cited 2018 Aug 20];8(8):1425–32. Available from: http://www.jcancer.org/v08p1425.htm
Menezes ME, Shen X-N, Das SK, Emdad L, Guo C, Yuan F, et al. decot functions as a tumor suppressor gene in vivo in transgenic mouse models of breast cancer. Oncotarget [Internet]. 2015 Nov 10 [cited 2018 Aug 20];6(35):36928–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26474456
Liikanen I, Tähtinen S, Guse K, Gutmann T, Savola P, Oksanen M, et al. Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer. Mol Cancer Ther [Internet]. 2016 Aug 17 [cited 2018 Aug 20];15(9):2259–69. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27458139
Ingemarsdotter CK, Tookman LA, Browne A, Pirlo K, Cutts R, Chelela C, et al. Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control. Mol Oncol [Internet]. 2015 Apr 1 [cited 2018 Aug 20];9(4):791–805. Available from: http://doi.wiley.com/10.1016/j.molonc.2014.12.007
Tan KX, Danquah MK, Sidhu A, Ongkudon CM, Lau SY. Towards targeted cancer therapy: Aptamer or oncolytic virus? Eur J Pharm Sci [Internet]. 2017 Jan 1 [cited 2018 Jul 29];96:8–19. Available from: https://www.sciencedirect.com/science/article/pii/S0928098716303505
Sanchez C. conociendo y comprendiendo la célula cancerosa: fisiopatología del cáncer. Rev medica Clin condes [Internet]. 2013;24:553–62. Available from: https://www.clinicalascondes.cl/Dev_CLC/media/Imagenes/PDF revista médica/2013/4 julio/REV--MED--CLIN.-CONDES---2013;-24(4)- WEB.pdf
Cooper GM, Hausman RE. La célula [Internet]. Marbán; 2014 [cited 2018 Aug 7]. Available from: https://www.librerianacional.com/pagina=producto&libro=315210&autor= 8832&editorial=2507
María Teresa Martín de Civetta, MC; Julio Domingo Civetta M. Carcinogénesis [Internet]. Vol. 53, Salud Pública de México. salud publica de mexico; 2011 [cited 2018 Mar 20]. 405-414 p. Available from: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0036- 36342011000500008
Hernández DE. BIOLOGÍA DEL CÁNCER DE MAMA De interés en oncología. Rev Venez Oncol [Internet]. 2016 [cited 2018 Mar 20];28(3):188–200. Available from: http://www.redalyc.org/pdf/3756/375645930010.pdf
Pardo Ramos C, Cendales Duarte R. Incidencia, mortalidad y prevalencia de Cáncer en Colombia 2007 - 2011. Inst Nac Cancerol [Internet]. 2015 [cited 2018 Mar 22];1:148. Available from: http://www.cancer.gov.co/files/libros/archivos/incidencia1.pdf
INSTITUTO NACIONAL DE CANCEROLOGÍA. El cáncer de mama: un problema creciente en Colombia. 2012 [cited 2018 Mar 22];4. Available from: http://www.cancer.gov.co/files/libros/archivos/95685f345e64aa9f0fece8a 589b5acc3_BOLETIN HECHOS Y ACCIONES MAMA.PDF
ersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol [Internet]. 2014 Aug 10 [cited 2018 Feb 20];5(3):412–24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25114856
A. Merino Bonillaa,∗ MTT y LHRM. El cáncer de mama en el siglo XXI: de la detección precoz a los nuevos tratamientos. Radiologia [Internet]. 2017 Sep 1 [cited 2017 Oct 12];59(5):368–79. Available from: http://www.sciencedirect.com/science/article/pii/S003383381730
Rakha EA, El-Sayed ME, Green AR, Paish EC, Powe DG, Gee J, et al. Biologic and Clinical Characteristics of Breast Cancer With Single Hormone Receptor–Positive Phenotype. J Clin Oncol [Internet]. 2007 Oct 20 [cited 2018 Mar 13];25(30):4772–8. Available from: http://ascopubs.org/doi/10.1200/JCO.2007.12.2747
Sotiriou C, Pusztai L. Gene-Expression Signatures in Breast Cancer. N Engl J Med [Internet]. 2009 Feb 19 [cited 2018 Mar 8];360(8):790–800. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMra0801289
Foulkes WD, Smith IE, Reis-Filho JS. Triple-Negative Breast Cancer. N Engl J Med [Internet]. 2010 Nov 11 [cited 2018 Mar 13];363(20):1938–48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21067385
Bourgeois-Daigneault M-C, Roy DG, Aitken AS, El Sayes N, Martin NT, Varette O, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med [Internet]. 2018 Jan 3 [cited 2018 Jul 29];10(422):eaao1641. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29298865
Arrechea Irigoyen MA, Vicente García F, Córdoba Iturriagagoitia A, Ibáñez Beroiz B, Santamaría Martínez M, Guillén Grima F. Subtipos moleculares del cáncer de mama: implicaciones pronósticas y características clínicas e inmunohistoquímicas. An Sist Sanit Navar [Internet]. 2011 Aug [cited 2018 Mar 13];34(2):219–33. Available from: http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1137- 66272011000200008&lng=en&nrm=iso&tlng=en
Escrivá-de-Romaní S, Arumí M, Bellet M, Saura C. HER2-positive breast cancer: Current and new therapeutic strategies. The Breast [Internet]. 2018 Jun 1 [cited 2018 Jul 29];39:80–8. Available from: https://www.sciencedirect.com/science/article/pii/S0960977618300547
Loibl S, Gianni L. HER2-positive breast cancer. Lancet [Internet]. 2017 Jun 17 [cited 2018 Jul 29];389(10087):2415–29. Available from: https://www.sciencedirect.com/science/article/pii/S0140673616324175
Martín M, Herrero A, Echavarría I, Echavarría I. El cáncer de mama. Arbor [Internet]. 2015 Jun 30 [cited 2018 Mar 8];191(773):a234. Available from: http://arbor.revistas.csic.es/index.php/arbor/article/view/2037/2530
Alonso Castellanos S, Soto Célix M, Alonso Galarreta J, Riego Valledor A del, Miján de la Torre A. Efectos adversos metabólicos y nutricionales asociados a la terapia biológica del cáncer. Nutr Hosp [Internet]. 2014 [cited 2018 Mar 22];29(2):259–68. Available from: http://scielo.isciii.es/scielo.php?pid=S0212- 16112014000200004&script=sci_arttext&tlng=pt
Eisenberg DP, Adusumilli PS, Hendershott KJ, Chung S, Yu Z, Chan M-K, et al. Real-time intraoperative detection of breast cancer axillary lymph node metastases using a green fluorescent protein-expressing herpes virus. Ann Surg [Internet]. 2006 Jun [cited 2018 Jul 29];243(6):824-30-2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16772786
Zhang W, Ge K, Zhao Q, Zhuang X, Deng Z, Liu L, et al. A novel oHSV-1 targeting telomerase reverse transcriptase-positive cancer cells via tumorspecific promoters regulating the expression of ICP4. Oncotarget [Internet]. 2015 Aug 21 [cited 2018 Aug 20];6(24):20345–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25972362
Teshigahara O, Goshima F, Takao K, Kohno S, Kimata H, Nakao A, et al. Oncolytic viral therapy for breast cancer with herpes simplex virus type 1 mutant HF 10. J Surg Oncol [Internet]. 2004 Jan [cited 2018 Jul 29];85(1):42–7. Available from: http://doi.wiley.com/10.1002/jso.20005
Kimata H, Imai T, Kikumori T, Teshigahara O, Nagasaka T, Goshima F, et al. Pilot Study of Oncolytic Viral Therapy Using Mutant Herpes Simplex Virus (HF10) Against Recurrent Metastatic Breast Cancer. Ann Surg Oncol [Internet]. 2006 Aug 24 [cited 2018 Jul 29];13(8):1078–84. Available from: http://www.springerlink.com/index/10.1245/ASO.2006.08.03
Marcato P, Dean CA, Giacomantonio CA, Lee PW. Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells. Mol Ther [Internet]. 2009 Jun 1 [cited 2018 Jul 29];17(6):972–9. Available from: https://www.sciencedirect.com/science/article/pii/S1525001616318032
Dong X, Qu W, Ma S, Zhu Z, Zheng C, He A, et al. Potent antitumoral effects of targeted promoter-driven oncolytic adenovirus armed with Dm-dNK for breast cancer in vitro and in vivo. Cancer Lett [Internet]. 2013 Jan 1 [cited 2018 Aug 20];328(1):95–103. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2300051
ang Y, Xu W, Neill T, Hu Z, Wang C-H, Xiao X, et al. Systemic Delivery of an Oncolytic Adenovirus Expressing Decorin for the Treatment of Breast Cancer Bone Metastases. Hum Gene Ther [Internet]. 2015 Dec 14 [cited 2018 Aug 20];26(12):813–25. Available from: http://www.liebertpub.com/doi/10.1089/hum.2015.098
Sarkar S, Quinn BA, Shen X-N, Dash R, Das SK, Emdad L, et al. Therapy of prostate cancer using a novel cancer terminator virus and a small molecule BH-3 mimetic. Oncotarget [Internet]. 2015 May 10 [cited 2018 Aug 20];6(13):10712–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25926554
Wang H, Chen NG, Minev BR, Szalay AA. Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells. J Transl Med [Internet]. 2012 Aug 17 [cited 2018 Jul 29];10(1):167. Available from: http://translationalmedicine.biomedcentral.com/articles/10.1186/1479-5876-10-167
Seubert CM, Stritzker J, Hess M, Donat U, Sturm JB, Chen N, et al. Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA. Cancer Gene Ther [Internet]. 2011 Jan [cited 2018 Aug 20];18(1):42–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20829890
Pugalenthi A, Mojica K, Ady JW, Johnsen C, Love D, Chen NG, et al. Recombinant vaccinia virus GLV-1h68 is a promising oncolytic vector in the treatment of cholangiocarcinoma. Cancer Gene Ther [Internet]. 2015 Dec 20 [cited 2018 Aug 20];22(12):591–6. Available from: http://www.nature.com/articles/cgt201560
Geekiyanage H, Galanis E. MiR-31 and miR-128 regulates poliovirus receptor-related 4 mediated measles virus infectivity in tumors. Mol Oncol [Internet]. 2016 Nov [cited 2018 Aug 20];10(9):1387–403. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27507538
Gil M, Seshadri M, Komorowski MP, Abrams SI, Kozbor D. Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases. Proc Natl Acad Sci U S A [Internet]. 2013 Apr 2 [cited 2018 Jul 29];110(14):E1291-300. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23509246
Gollamudi R, Ghalib MH, Desai KK, Chaudhary I, Wong B, Einstein M, et al. Intravenous administration of Reolysin®, a live replication competent RNA virus is safe in patients with advanced solid tumors. Invest New Drugs [Internet]. 2010 Oct 2 [cited 2018 Aug 20];28(5):641–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19572105
Norman KL, Coffey MC, Hirasawa K, Demetrick DJ, Nishikawa SG, DiFrancesco LM, et al. Reovirus Oncolysis of Human Breast Cancer. https://home.liebertpub.com/hum [Internet]. 2004 Jul 6 [cited 2018 Jul 29]; Available from: https://www.liebertpub.com/doi/abs/10.1089/10430340252837233
Duchnowska R, Loibl S, Jassem J. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treat Rev [Internet]. 2018 Jun 1 [cited 2018 Jul 29];67:71–7. Available from: https://www.sciencedirect.com/science/article/pii/S0305737218300677
Le Boeuf F, Selman M, Son HH, Bergeron A, Chen A, Tsang J, et al. Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma. Int J Cancer [Internet]. 2017 Sep 15 [cited 2018 Aug 20];141(6):1257–64. Available from: http://doi.wiley.com/10.1002/ijc.30813
Janke M, Peeters B, de Leeuw O, Moorman R, Arnold A, Fournier P, et al. Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy. Gene Ther [Internet]. 2007 Dec 4 [cited 2018 Aug 20];14(23):1639–49. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17914407
Ju J, Zhu A-J, Yuan P. Progress in targeted therapy for breast cancer. Chronic Dis Transl Med [Internet]. 2018 Jul 7 [cited 2018 Jul 29]; Available from: https://www.sciencedirect.com/science/article/pii/S2095882X18300069
Hamano S, Mori Y, Aoyama M, Kataoka H, Tanaka M, Ebi M, et al. Oncolytic reovirus combined with trastuzumab enhances antitumor efficacy through TRAIL signaling in human HER2-positive gastric cancer cells. Cancer Lett [Internet]. 2015 Jan 28 [cited 2018 Aug 20];356(2):846–54. Available from: https://www.sciencedirect.com/science/article/pii/S0304383514006806
Li J, Zeng W, Huang Y, Zhang Q, Hu P, Rabkin SD, et al. Treatment of breast cancer stem cells with oncolytic herpes simplex virus. Cancer Gene Ther [Internet]. 2012 Oct 17 [cited 2018 Jul 29];19(10):707–14. Available from: http://www.nature.com/articles/cgt201249
Seth P, Wang Z-G, Pister A, Zafar MB, Kim S, Guise T, et al. Development of Oncolytic Adenovirus Armed with a Fusion of Soluble Transforming Growth Factor-β Receptor II and Human Immunoglobulin Fc for Breast Cancer Therapy. Hum Gene Ther [Internet]. 2006 Nov 16 [cited 2018 Jul 29];17(11):1152–61. Available from: http://www.liebertonline.com/doi/abs/10.1089/hum.2006.17.1152
Zhu W, Zhang H, Shi Y, Song M, Zhu B, Wei L. Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast cancer. Cancer Biol Ther [Internet]. 2013 Nov [cited 2018 Aug 20];14(11):1016–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24025362
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spelling Hernández, Edith del Carmenbd29ccc2004fadfb8fe30138a4f683f7Rodríguez Panduro, Mauricio Humberto5a3aa353075aff39d48a3977c88cdb07Buitrago Mejía, Lorenab3bac40997eb347d81e20cde6b9182742022-03-07T20:25:15Z2022-03-07T20:25:15Z2018-11https://repositorio.unicolmayor.edu.co/handle/unicolmayor/478158661Los virus oncolíticos son virus naturales o genéticamente modificados que tienen la capacidad de infectar las células cancerígenas, replicarse dentro de ellas causando su destrucción y de esta manera estimular la respuesta antitumoral del huésped. Por otra parte el cáncer de mama es de gran importancia en salud pública con un número de casos que crece a través del tiempo. Dentro de su clasificación se encuentra el cáncer de mama HER2 positivo que es de mal pronóstico, agresivo y de alto grado histológico alto, que incrementa con el diagnóstico tardío. En esta revisión bibliográfica se recopiló información significativa sobre los virus oncolíticos y su posible empleabilidad en el tratamiento de cáncer de mama, descripción de su potencial, y los diferentes mecanismos de acción que los hacen agentes biológicos excelentes en terapias anti cáncer. Los resultados arrojan que la mayoría de investigaciones con virus oncolíticos se realizan en EEUU, y los virus más empleados para ensayos cáncer de mama son el virus del herpes simplex con un 31% y el adenovirus con un 13%; estos virus modificados permiten activar el sistema inmune, aumentar la selectividad hacia la célula tumoral, promover la creación de anticuerpos contra un blanco especifico, ser útiles como marcadores de seguimiento, entre otros. Con esta revisión de literatura se espera motivar a los investigadores a incrementar sus ensayos no solo con otros virus oncolíticos sino también con diferentes blancos terapéuticos en el cáncer de mama que permitan ampliar las opciones terapéuticas en los pacientes, en especial el cáncer de mama HER2 positivo. Que si bien, de acuerdo a esta revisión para cáncer de mama HER2 positivo no hay una muestra representativa de experimentos que ayuden a concluir si es o no factible una alternativa terapéutica con virus oncolíticos.1. INTRODUCCIÓN 1 2. DESCRIPCIÓN DEL PROYECTO 2 2.1 Planteamiento del Problema 2 2.2 Justificación 3 3. OBJETIVOS 4 3.1 GENERAL 4 3.2 ESPECÍFICOS 4 4. ANTECEDENTES 5 5. MARCO TEORICO 8 5.1 Virus oncolíticos. 8 5.1.1 Mecanismo de acción de los virus oncolíticos 9 5.1.2 Usos actuales de los virus oncolíticos 12 5.2 Definición de cáncer 16 5.3 El Cáncer de mama 18 5.3.1 Definición del cáncer de mama 18 5.3.2 Epidemiología del Cáncer de mama 18 5.3.3 Clasificación molecular del Cáncer de mama 22 5.3.4 Cáncer de mama HER2 Positivo 23 5.3.5 Tratamiento para el Cáncer de mama 24 5.3.5.1Tratamiento farmacológico tradicional 24 5.3.5.2Tratamiento con virus oncolíticos 26 6. METODOLOGÍA 29 6.1 Diseño Metodológico 29 6.2 Procedimientos 29 6.2.1 Búsqueda de la información 29 6.2.2 Recolección de la información 29 6.2.3 Análisis de la información 29 7. RESULTADOS 30 7.1 Año de Publicación 30 7.2 Tipo de publicación 31 7.3 País de publicación 32 7.4 Tema de las publicaciones 33 7.5 Virus empleados en investigación para el tratamiento del cáncer 34 7.6 Uso de los virus oncolíticos en Cáncer de mama y otros tipos de cáncer 35 7.7 Tipos de virus oncolíticos empleados en investigación para cáncer de mama 36 7.8 Mecanismos de acción de los virus del herpes simplex para cáncer de mama 37 7.9 Mecanismos de acción de los adenovirus para cáncer de mama 39 8. DISCUSIÓN 41 9. CONCLUSIONES 44PregradoBacteriólogo(a) y Laboratorista Clínico55p.application/pdfspaUniversidad Colegio Mayor de CundinamarcaFacultad de Ciencias de la SaludBogotá D.CBacteriología y Laboratorio ClínicoDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2018https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/closedAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_14cbRevisión de literatura sobre los virus con posible capacidad oncolítica para el tratamiento del cáncer de mama Her2 positivoTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPinfo:eu-repo/semantics/publishedVersionMINSALUD. Cáncer de mama, una enfermedad en ascenso en Colombia [Internet]. 2014 [cited 2018 Mar 20]. Available from: https://www.minsalud.gov.co/Paginas/-Cancer-de-mama,-unaenfermedad-en-ascenso-en-Colombia.aspxViviana Y, Márquez A, Balcázar IB, Aristizábal FA. Tratamiento de cáncer de seno y farmacogenética Treatment of breast cancer and pharmacogenetics. Rev Colomb Biotecnol [Internet]. 2016 [cited 2018 Feb 20]; Available from: http://www.scielo.org.co/pdf/biote/v18n1/v18n1a14.pdfMcCafferty MPJ, Healy NA, Kerin MJ. Breast cancer subtypes and molecular biomarkers. Diagnostic Histopathol [Internet]. 2009 Oct 1 [cited 2017 Oct 26];15(10):485–9. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1756231709001455D MK, S A-D. Efectos del Trastuzumab como Terapia Coadyuvante para Pacientes con Cáncer de Mama Her2-Positivo: Una Revisión Sistemática. Arch Med [Internet]. 2017 Aug 5 [cited 2017 Oct 27];13(3). Available from: http://www.archivosdemedicina.com/medicina-de-familia/efectos-deltrastuzumab-como-terapia-coadyuvante-para-pacientes-con-caacutencerde-mama-her2positivo-una-revisioacuten-sistemaacut.php?aid=20055Garnock-Jones KP, Keating GM, Scott LJ. Trastuzumab. Drugs [Internet]. 2010 Jan [cited 2017 Oct 27];70(2):215–39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20108993Arrese I, González P, Miranda P, Perez-Nuñez P, Pascual B, Lobato RD. Tratamiento de los gliomas mediante virus oncolíticos: revisión de la literatura. Neurocirugia. 2005;16:158–68.Rodríguez L. CAGF. LA PROTEÍNA VIRAL VP6 DE ROTAVIRUS COINMUNOPRECIPITA CON HSC70 EN CÉLULAS MA104. 2006;Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther [Internet]. 2007;15(4):651–9. Available from: http://dx.doi.org/10.1038/sj.mt.6300108jaime R. merchan barros, jun j. madera merchan sheila p. auz ramirez. viroterapia mediante virus oncoliticos en tumores sólidos [Internet]. 2011. Available from: http://medpre.med.ec/secciones/medicina/1 revista/Viroterapia mediante virus oncoliticos en tumores solidos.pdfRamos Guette PL. Características clínicas y mortalidad en pacientes con cáncer de mama avanzado (estados iiia iiib iiic) en colombia, clínica oncocare, 2003–2012. Rev Colomb Cancerol [Internet]. 2013 Dec 1 [cited 2018 Mar 8];17(4):180–1. Available from: https://www.sciencedirect.com/science/article/pii/S0123901513702002Rodríguez JA, Martínez LM, Cruz N, Cómbita AL. Terapia génica para el tratamiento del cáncer. Rev Colomb Cancerol [Internet]. 2014;18(1):27– 40. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0123901514702227Cho M. Bioinformatics research on the specificity and safety of oncolytic viruses. 2015 [cited 2017 Oct 13]; Available from: http://sspace.snu.ac.kr/handle/10371/128348Dutilh BE, Reyes A, Hall RJ, Whiteson KL. Editorial: Virus Discovery by Metagenomics: The (Im)possibilities. Front Microbiol [Internet]. 2017 Sep 8 [cited 2017 Sep 26];8:1710. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28943867Lawler SE, Speranza M-C, Cho C-F, Chiocca EA, RL M, BD L, et al. Oncolytic Viruses in Cancer Treatment. JAMA Oncol [Internet]. 2016;2(12):938–50. Available from: http://oncology.jamanetwork.com/article.aspx?doi=10.1001/jamaoncol.2 016.2064Suryawanshi YR, Zhang T, Essani K. Oncolytic viruses: emerging options for the treatment of breast cancer. Med Oncol [Internet]. 2017 Mar 9 [cited 2018 Mar 15];34(3):43. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28185165Miest TS, Cattaneo R. New viruses for cancer therapy: meeting clinical needs. Nat Rev Microbiol [Internet]. 2014 Jan 2 [cited 2018 Aug 13];12(1):23–34. Available from: http://www.nature.com/articles/nrmicro3140Release FDAN, Release FI. FDA approves first of its kind product for the treatment of melanoma. 2016;1–4. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm54 8278.htmBramante S, Koski A, Liikanen I, Vassilev L, Oksanen M, Siurala M, et al. Oncolytic virotherapy for treatment of breast cancer, including triplenegative breast cancer. Oncoimmunology [Internet]. 2016 Feb [cited 2018 Aug 20];5(2):e1078057. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27057453Talimogene laherparepvec for melanoma. Aust Prescr [Internet]. 2017 Feb [cited 2018 Mar 15];40(1):38–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28246438Hummel JL, Safroneeva E, Mossman KL. The role of ICP0-Null HSV-1 and interferon signaling defects in the effective treatment of breast adenocarcinoma. Mol Ther [Internet]. 2005 Dec [cited 2018 Aug 22];12(6):1101–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16140040Sahin TT, Kasuya H, Nomura N, Shikano T, Yamamura K, Gewen T, et al. Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer. Cancer Gene Ther [Internet]. 2012 Apr 23 [cited 2018 Mar 16];19(4):229–37. Available from: http://www.nature.com/articles/cgt201180Thomas DL, Fraser NW. HSV-1 therapy of primary tumors reduces the number of metastases in an immune-competent model of metastatic breast cancer. Mol Ther [Internet]. 2003 Oct 1 [cited 2018 Jul 29];8(4):543–51. Available from: https://www.sciencedirect.com/science/article/pii/S1525001603002363Cody JJ, Markert JM, Hurst DR. Histone Deacetylase Inhibitors Improve the Replication of Oncolytic Herpes Simplex Virus in Breast Cancer Cells. PLoS One [Internet]. 2014 [cited 2018 Jul 29];9(3):e92919. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092919Chen X, Han J, Chu J, Zhang L, Zhang J, Chen C, et al. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases. Oncotarget [Internet]. 2016 May 10 [cited 2018 Jul 29];7(19):27764–77. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27050072Walker JD, Sehgal I, Kousoulas KG. Oncolytic herpes simplex virus 1 encoding 15-prostaglandin dehydrogenase mitigates immune suppression and reduces ectopic primary and metastatic breast cancer in mice. J Virol [Internet]. 2011 Jul [cited 2018 Aug 22];85(14):7363–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21543507Fasullo M, Burch A, Britton A. Hypoxia enhances the replication of oncolytic herpes simplex virus in p53- breast cancer cells. Cell Cycle [Internet]. 2009 Jul 15 [cited 2018 Jul 29];8(14):2194–7. Available from: http://www.tandfonline.com/doi/abs/10.4161/cc.8.14.8934Pourchet A, Fuhrmann SR, Pilones KA, Demaria S, Frey AB, Mulvey M, et al. CD8+ T-cell Immune Evasion Enables Oncolytic Virus Immunotherapy. EBioMedicine [Internet]. 2016 Mar 1 [cited 2018 Aug 20];5:59–67. Available from: https://www.sciencedirect.com/science/article/pii/S2352396416300184Tan G, Kasuya H, Sahin TT, Yamamura K, Wu Z, Koide Y, et al. Combination therapy of oncolytic herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft. Int J Cancer [Internet]. 2015 Apr 1 [cited 2018 Aug 20];136(7):1718–30. Available from: http://doi.wiley.com/10.1002/ijc.29163Chiocca EA. Oncolytic viruses. Invest New Drugs [Internet]. 2002;17(4):375–86. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12459732Hirvinen M, Rajecki M, Kapanen M, Parviainen S, Rouvinen-Lagerström N, Diaconu I, et al. Immunological Effects of a Tumor Necrosis Factor Alpha– Armed Oncolytic Adenovirus. Hum Gene Ther [Internet]. 2015 Mar 4 [cited 2018 Aug 20];26(3):134–44. Available from: http://www.liebertpub.com/doi/10.1089/hum.2014.0691Jiang H, Rivera-Molina Y, Gomez-Manzano C, Clise-Dwyer K, Bover L, Vence LM, et al. Therapeutics, Targets, and Chemical Biology Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination. Cancer Res [Internet]. 2017 [cited 2018 Aug 20];77(14). Available from: http://cancerres.aacrjournals.org/Hock K, Laengle J, Kuznetsova I, Egorov A, Hegedus B, Dome B, et al. Oncolytic influenza A virus expressing interleukin-15 decreases tumor growth in vivo. Surgery [Internet]. 2017 Mar 1 [cited 2018 Jul 29];161(3):735–46. Available from: https://www.sciencedirect.com/science/article/pii/S0039606016304809Stoff-Khalili MA, Rivera AA, Mathis JM, Banerjee NS, Moon AS, Hess A, et al. Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma. Breast Cancer Res Treat [Internet]. 2007 Aug 31 [cited 2018 Jul 29];105(2):157–67. Available from: http://link.springer.com/10.1007/s10549-006-9449-8Bazan-Peregrino M, Carlisle RC, Hernandez-Alcoceba R, Iggo R, Homicsko K, Fisher KD, et al. Comparison of Molecular Strategies for Breast Cancer Virotherapy Using Oncolytic Adenovirus. https://home.liebertpub.com/hum [Internet]. 2008 Sep 16 [cited 2018 Jul 29]; Available from: https://www.liebertpub.com/doi/abs/10.1089/hum.2008.047Gomes EM, Rodrigues MS, Phadke AP, Butcher LD, Starling C, Chen S, et al. Antitumor Activity of an Oncolytic Adenoviral-CD40 Ligand (CD154) Transgene Construct in Human Breast Cancer Cells. 2009 [cited 2018 Jul 29]; Available from: www.aacrjournals.orgGentschev I, Stritzker J, Hofmann E, Weibel S, Yu YA, Chen N, et al. Use of an oncolytic vaccinia virus for the treatment of canine breast cancer in nude mice: preclinical development of a therapeutic agent. Cancer Gene Ther [Internet]. 2009 Apr 24 [cited 2018 Jul 29];16(4):320–8. Available from: http://www.nature.com/articles/cgt200887Yoo SY, Bang SY, Jeong S-N, Kang DH, Heo J. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer. Oncotarget [Internet]. 2016 Mar 29 [cited 2018 Aug 20];7(13):16479–89. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26918725Gholami S, Marano A, Chen NG, Aguilar RJ, Frentzen A, Chen C-H, et al. A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer. Breast Cancer Res Treat [Internet]. 2014 Dec 13 [cited 2018 Aug 20];148(3):489–99. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25391896Sugiyama T, Yoneda M, Kuraishi T, Hattori S, Inoue Y, Sato H, et al. Measles virus selectively blind to signaling lymphocyte activation molecule as a novel oncolytic virus for breast cancer treatment. Gene Ther [Internet]. 2013 Mar 21 [cited 2018 Jul 29];20(3):338–47. Available from: http://www.nature.com/articles/gt201244Iankov ID, Msaouel P, Allen C, Federspiel MJ, Bulur PA, Dietz AB, et al. Demonstration of anti-tumor activity of oncolytic measles virus strains in a malignant pleural effusion breast cancer model. Breast Cancer Res Treat [Internet]. 2010 Aug 6 [cited 2018 Jul 29];122(3):745–54. Available from: http://link.springer.com/10.1007/s10549-009-0602-zMcDonald CJ, Erlichman C, Ingle JN, Rosales GA, Allen C, Greiner SM, et al. A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer. Breast Cancer Res Treat [Internet]. 2006 Sep 27 [cited 2018 Jul 29];99(2):177–84. Available from: http://link.springer.com/10.1007/s10549-006-9200-5Asada T. Treatment of human cancer with mumps virus. Cancer [Internet]. 1974 Dec [cited 2018 Aug 7];34(6):1907–28. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4611607Ammayappan A, Russell SJ, Federspiel MJ. Recombinant mumps virus as a cancer therapeutic agent. Mol Ther - Oncolytics [Internet]. 2016 Jan 1 [cited 2018 Jul 29];3. Available from: https://www.sciencedirect.com/science/article/pii/S2372770517300128Le Boeuf F, Gebremeskel S, McMullen N, He H, Greenshields AL, Hoskin DW, et al. Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models. Mol Ther - Oncolytics [Internet]. 2017 Sep 15 [cited 2018 Jul 29];6:80–9. Available from: https://www.sciencedirect.com/science/article/pii/S237277051730030XOlagnier D, Lababidi RR, Hadj SB, Sze A, Liu Y, Naidu SD, et al. Activation of Nrf2 Signaling Augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity. Mol Ther [Internet]. 2017 Aug 2 [cited 2018 Aug 20];25(8):1900–16. Available from: https://www.sciencedirect.com/science/article/pii/S152500161730206XBourgeois-Daigneault M-C, Roy DG, Falls T, Twumasi-Boateng K, StGermain LE, Marguerie M, et al. Oncolytic vesicular stomatitis virus expressing interferon-σ has enhanced therapeutic activity. Mol Ther - Oncolytics [Internet]. 2016 Jan 1 [cited 2018 Aug 20];3. Available from: https://www.sciencedirect.com/science/article/pii/S237277051630033XPlatonov ME, Borovjagin A V., Kaverina N, Xiao T, Kadagidze Z, Lesniak M, et al. KISS1 tumor suppressor restricts angiogenesis of breast cancer brain metastases and sensitizes them to oncolytic virotherapy in vitro. Cancer Lett [Internet]. 2018 Mar 28 [cited 2018 Jul 29];417:75–88. Available from: https://www.sciencedirect.com/science/article/pii/S0304383517307966Sakhawat A, Liu Y, Ma L, Muhammad T, Wang S, Zhang L, et al. Upregulation of Coxsackie Adenovirus Receptor Sensitizes Cisplatin-Resistant Lung Cancer Cells to CRAd-Induced Inhibition. J Cancer [Internet]. 2017 [cited 2018 Aug 20];8(8):1425–32. Available from: http://www.jcancer.org/v08p1425.htmMenezes ME, Shen X-N, Das SK, Emdad L, Guo C, Yuan F, et al. decot functions as a tumor suppressor gene in vivo in transgenic mouse models of breast cancer. Oncotarget [Internet]. 2015 Nov 10 [cited 2018 Aug 20];6(35):36928–42. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26474456Liikanen I, Tähtinen S, Guse K, Gutmann T, Savola P, Oksanen M, et al. Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer. Mol Cancer Ther [Internet]. 2016 Aug 17 [cited 2018 Aug 20];15(9):2259–69. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27458139Ingemarsdotter CK, Tookman LA, Browne A, Pirlo K, Cutts R, Chelela C, et al. Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control. Mol Oncol [Internet]. 2015 Apr 1 [cited 2018 Aug 20];9(4):791–805. Available from: http://doi.wiley.com/10.1016/j.molonc.2014.12.007Tan KX, Danquah MK, Sidhu A, Ongkudon CM, Lau SY. Towards targeted cancer therapy: Aptamer or oncolytic virus? Eur J Pharm Sci [Internet]. 2017 Jan 1 [cited 2018 Jul 29];96:8–19. Available from: https://www.sciencedirect.com/science/article/pii/S0928098716303505Sanchez C. conociendo y comprendiendo la célula cancerosa: fisiopatología del cáncer. Rev medica Clin condes [Internet]. 2013;24:553–62. Available from: https://www.clinicalascondes.cl/Dev_CLC/media/Imagenes/PDF revista médica/2013/4 julio/REV--MED--CLIN.-CONDES---2013;-24(4)- WEB.pdfCooper GM, Hausman RE. La célula [Internet]. Marbán; 2014 [cited 2018 Aug 7]. Available from: https://www.librerianacional.com/pagina=producto&libro=315210&autor= 8832&editorial=2507María Teresa Martín de Civetta, MC; Julio Domingo Civetta M. Carcinogénesis [Internet]. Vol. 53, Salud Pública de México. salud publica de mexico; 2011 [cited 2018 Mar 20]. 405-414 p. Available from: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0036- 36342011000500008Hernández DE. BIOLOGÍA DEL CÁNCER DE MAMA De interés en oncología. Rev Venez Oncol [Internet]. 2016 [cited 2018 Mar 20];28(3):188–200. Available from: http://www.redalyc.org/pdf/3756/375645930010.pdfPardo Ramos C, Cendales Duarte R. Incidencia, mortalidad y prevalencia de Cáncer en Colombia 2007 - 2011. Inst Nac Cancerol [Internet]. 2015 [cited 2018 Mar 22];1:148. Available from: http://www.cancer.gov.co/files/libros/archivos/incidencia1.pdfINSTITUTO NACIONAL DE CANCEROLOGÍA. El cáncer de mama: un problema creciente en Colombia. 2012 [cited 2018 Mar 22];4. Available from: http://www.cancer.gov.co/files/libros/archivos/95685f345e64aa9f0fece8a 589b5acc3_BOLETIN HECHOS Y ACCIONES MAMA.PDFersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol [Internet]. 2014 Aug 10 [cited 2018 Feb 20];5(3):412–24. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25114856A. Merino Bonillaa,∗ MTT y LHRM. El cáncer de mama en el siglo XXI: de la detección precoz a los nuevos tratamientos. Radiologia [Internet]. 2017 Sep 1 [cited 2017 Oct 12];59(5):368–79. Available from: http://www.sciencedirect.com/science/article/pii/S003383381730Rakha EA, El-Sayed ME, Green AR, Paish EC, Powe DG, Gee J, et al. Biologic and Clinical Characteristics of Breast Cancer With Single Hormone Receptor–Positive Phenotype. J Clin Oncol [Internet]. 2007 Oct 20 [cited 2018 Mar 13];25(30):4772–8. Available from: http://ascopubs.org/doi/10.1200/JCO.2007.12.2747Sotiriou C, Pusztai L. Gene-Expression Signatures in Breast Cancer. N Engl J Med [Internet]. 2009 Feb 19 [cited 2018 Mar 8];360(8):790–800. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMra0801289Foulkes WD, Smith IE, Reis-Filho JS. Triple-Negative Breast Cancer. N Engl J Med [Internet]. 2010 Nov 11 [cited 2018 Mar 13];363(20):1938–48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21067385Bourgeois-Daigneault M-C, Roy DG, Aitken AS, El Sayes N, Martin NT, Varette O, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med [Internet]. 2018 Jan 3 [cited 2018 Jul 29];10(422):eaao1641. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29298865Arrechea Irigoyen MA, Vicente García F, Córdoba Iturriagagoitia A, Ibáñez Beroiz B, Santamaría Martínez M, Guillén Grima F. Subtipos moleculares del cáncer de mama: implicaciones pronósticas y características clínicas e inmunohistoquímicas. An Sist Sanit Navar [Internet]. 2011 Aug [cited 2018 Mar 13];34(2):219–33. Available from: http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1137- 66272011000200008&lng=en&nrm=iso&tlng=enEscrivá-de-Romaní S, Arumí M, Bellet M, Saura C. HER2-positive breast cancer: Current and new therapeutic strategies. The Breast [Internet]. 2018 Jun 1 [cited 2018 Jul 29];39:80–8. Available from: https://www.sciencedirect.com/science/article/pii/S0960977618300547Loibl S, Gianni L. HER2-positive breast cancer. Lancet [Internet]. 2017 Jun 17 [cited 2018 Jul 29];389(10087):2415–29. Available from: https://www.sciencedirect.com/science/article/pii/S0140673616324175Martín M, Herrero A, Echavarría I, Echavarría I. El cáncer de mama. Arbor [Internet]. 2015 Jun 30 [cited 2018 Mar 8];191(773):a234. Available from: http://arbor.revistas.csic.es/index.php/arbor/article/view/2037/2530Alonso Castellanos S, Soto Célix M, Alonso Galarreta J, Riego Valledor A del, Miján de la Torre A. Efectos adversos metabólicos y nutricionales asociados a la terapia biológica del cáncer. Nutr Hosp [Internet]. 2014 [cited 2018 Mar 22];29(2):259–68. Available from: http://scielo.isciii.es/scielo.php?pid=S0212- 16112014000200004&script=sci_arttext&tlng=ptEisenberg DP, Adusumilli PS, Hendershott KJ, Chung S, Yu Z, Chan M-K, et al. Real-time intraoperative detection of breast cancer axillary lymph node metastases using a green fluorescent protein-expressing herpes virus. Ann Surg [Internet]. 2006 Jun [cited 2018 Jul 29];243(6):824-30-2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16772786Zhang W, Ge K, Zhao Q, Zhuang X, Deng Z, Liu L, et al. A novel oHSV-1 targeting telomerase reverse transcriptase-positive cancer cells via tumorspecific promoters regulating the expression of ICP4. Oncotarget [Internet]. 2015 Aug 21 [cited 2018 Aug 20];6(24):20345–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25972362Teshigahara O, Goshima F, Takao K, Kohno S, Kimata H, Nakao A, et al. Oncolytic viral therapy for breast cancer with herpes simplex virus type 1 mutant HF 10. J Surg Oncol [Internet]. 2004 Jan [cited 2018 Jul 29];85(1):42–7. Available from: http://doi.wiley.com/10.1002/jso.20005Kimata H, Imai T, Kikumori T, Teshigahara O, Nagasaka T, Goshima F, et al. Pilot Study of Oncolytic Viral Therapy Using Mutant Herpes Simplex Virus (HF10) Against Recurrent Metastatic Breast Cancer. Ann Surg Oncol [Internet]. 2006 Aug 24 [cited 2018 Jul 29];13(8):1078–84. Available from: http://www.springerlink.com/index/10.1245/ASO.2006.08.03Marcato P, Dean CA, Giacomantonio CA, Lee PW. Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells. Mol Ther [Internet]. 2009 Jun 1 [cited 2018 Jul 29];17(6):972–9. Available from: https://www.sciencedirect.com/science/article/pii/S1525001616318032Dong X, Qu W, Ma S, Zhu Z, Zheng C, He A, et al. Potent antitumoral effects of targeted promoter-driven oncolytic adenovirus armed with Dm-dNK for breast cancer in vitro and in vivo. Cancer Lett [Internet]. 2013 Jan 1 [cited 2018 Aug 20];328(1):95–103. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2300051ang Y, Xu W, Neill T, Hu Z, Wang C-H, Xiao X, et al. Systemic Delivery of an Oncolytic Adenovirus Expressing Decorin for the Treatment of Breast Cancer Bone Metastases. Hum Gene Ther [Internet]. 2015 Dec 14 [cited 2018 Aug 20];26(12):813–25. Available from: http://www.liebertpub.com/doi/10.1089/hum.2015.098Sarkar S, Quinn BA, Shen X-N, Dash R, Das SK, Emdad L, et al. Therapy of prostate cancer using a novel cancer terminator virus and a small molecule BH-3 mimetic. Oncotarget [Internet]. 2015 May 10 [cited 2018 Aug 20];6(13):10712–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25926554Wang H, Chen NG, Minev BR, Szalay AA. Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells. J Transl Med [Internet]. 2012 Aug 17 [cited 2018 Jul 29];10(1):167. Available from: http://translationalmedicine.biomedcentral.com/articles/10.1186/1479-5876-10-167Seubert CM, Stritzker J, Hess M, Donat U, Sturm JB, Chen N, et al. Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA. Cancer Gene Ther [Internet]. 2011 Jan [cited 2018 Aug 20];18(1):42–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20829890Pugalenthi A, Mojica K, Ady JW, Johnsen C, Love D, Chen NG, et al. Recombinant vaccinia virus GLV-1h68 is a promising oncolytic vector in the treatment of cholangiocarcinoma. Cancer Gene Ther [Internet]. 2015 Dec 20 [cited 2018 Aug 20];22(12):591–6. Available from: http://www.nature.com/articles/cgt201560Geekiyanage H, Galanis E. MiR-31 and miR-128 regulates poliovirus receptor-related 4 mediated measles virus infectivity in tumors. Mol Oncol [Internet]. 2016 Nov [cited 2018 Aug 20];10(9):1387–403. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27507538Gil M, Seshadri M, Komorowski MP, Abrams SI, Kozbor D. Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases. Proc Natl Acad Sci U S A [Internet]. 2013 Apr 2 [cited 2018 Jul 29];110(14):E1291-300. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23509246Gollamudi R, Ghalib MH, Desai KK, Chaudhary I, Wong B, Einstein M, et al. Intravenous administration of Reolysin®, a live replication competent RNA virus is safe in patients with advanced solid tumors. Invest New Drugs [Internet]. 2010 Oct 2 [cited 2018 Aug 20];28(5):641–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19572105Norman KL, Coffey MC, Hirasawa K, Demetrick DJ, Nishikawa SG, DiFrancesco LM, et al. Reovirus Oncolysis of Human Breast Cancer. https://home.liebertpub.com/hum [Internet]. 2004 Jul 6 [cited 2018 Jul 29]; Available from: https://www.liebertpub.com/doi/abs/10.1089/10430340252837233Duchnowska R, Loibl S, Jassem J. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treat Rev [Internet]. 2018 Jun 1 [cited 2018 Jul 29];67:71–7. Available from: https://www.sciencedirect.com/science/article/pii/S0305737218300677Le Boeuf F, Selman M, Son HH, Bergeron A, Chen A, Tsang J, et al. Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma. Int J Cancer [Internet]. 2017 Sep 15 [cited 2018 Aug 20];141(6):1257–64. Available from: http://doi.wiley.com/10.1002/ijc.30813Janke M, Peeters B, de Leeuw O, Moorman R, Arnold A, Fournier P, et al. Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy. Gene Ther [Internet]. 2007 Dec 4 [cited 2018 Aug 20];14(23):1639–49. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17914407Ju J, Zhu A-J, Yuan P. Progress in targeted therapy for breast cancer. Chronic Dis Transl Med [Internet]. 2018 Jul 7 [cited 2018 Jul 29]; Available from: https://www.sciencedirect.com/science/article/pii/S2095882X18300069Hamano S, Mori Y, Aoyama M, Kataoka H, Tanaka M, Ebi M, et al. Oncolytic reovirus combined with trastuzumab enhances antitumor efficacy through TRAIL signaling in human HER2-positive gastric cancer cells. Cancer Lett [Internet]. 2015 Jan 28 [cited 2018 Aug 20];356(2):846–54. Available from: https://www.sciencedirect.com/science/article/pii/S0304383514006806Li J, Zeng W, Huang Y, Zhang Q, Hu P, Rabkin SD, et al. Treatment of breast cancer stem cells with oncolytic herpes simplex virus. Cancer Gene Ther [Internet]. 2012 Oct 17 [cited 2018 Jul 29];19(10):707–14. Available from: http://www.nature.com/articles/cgt201249Seth P, Wang Z-G, Pister A, Zafar MB, Kim S, Guise T, et al. Development of Oncolytic Adenovirus Armed with a Fusion of Soluble Transforming Growth Factor-β Receptor II and Human Immunoglobulin Fc for Breast Cancer Therapy. Hum Gene Ther [Internet]. 2006 Nov 16 [cited 2018 Jul 29];17(11):1152–61. Available from: http://www.liebertonline.com/doi/abs/10.1089/hum.2006.17.1152Zhu W, Zhang H, Shi Y, Song M, Zhu B, Wei L. Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast cancer. Cancer Biol Ther [Internet]. 2013 Nov [cited 2018 Aug 20];14(11):1016–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24025362Virus naturalesCélulasCáncerCáncerRespuesta inmuneVirus oncolíticosTEXTINFORME FINAL nov 2018.pdf.txtINFORME FINAL nov 2018.pdf.txtExtracted texttext/plain99837https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/4781/5/INFORME%20FINAL%20nov%202018.pdf.txt9b97db094ae9043c5e16d279a79563f2MD55open accessINFORME FINAL nov 2018 FORMATO DERECHOS DE AUTOR.pdf.txtINFORME FINAL nov 2018 FORMATO DERECHOS DE AUTOR.pdf.txtExtracted texttext/plain20https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/4781/7/INFORME%20FINAL%20nov%202018%20FORMATO%20DERECHOS%20DE%20AUTOR.pdf.txt5d6646b4a6233434c923392559315771MD57metadata only accessPresentación lorena buitrago noviembre 2018.pdf.txtPresentación lorena buitrago noviembre 2018.pdf.txtExtracted 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Unicolmayorrepositorio@unicolmayor.edu.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