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Analysis of genetics determinants intrinsic to the tumor cells related to the heterogenous response to chemotherapy in a mouse model of ERBB2 breast cancer

AutorBlanco-Gómez, Adrián; Sáez-Freire, María del Mar; Castillo, Sonia ; Hontecillas-Prieto, Lourdes; Hernández Mulas, M. Luz; García-Cenador, Begoña; García-Criado, Francisco Javier; Mao, Jian-Hua; Galindo-Villardón, Purificación; Castellanos-Martín, Andrés; Pérez-Losada, J.
Fecha de publicación2015
CitaciónEACR-OECI Conference (2015)
ResumenAn essential aspect of breast cancer is its different evolution among patients with the same histopathological disease. Moreover, cancer is a tissue growing in the context of a complex organism, thus it can be identified two main sources of variability responsible for the disease behavior: intrinsic and extrinsic factors which act, respectively, mainly inside the tumor cells and outside them at local or systemic levels. Our aim is to identify intrinsic factors to the tumor cells responsible for the different responses of breast cancer to chemotherapy with Doxorubicin and Docetaxel. For this purpose, we collected tumors developed in a cohort of genetically heterogeneous mice from a backcross between a resistant strain to breast cáncer (C57BL/6) and a susceptible one (FVB) which overexpress the cNeu/ErbB2 protooncogene controlled by the MMTV prometer. The backcross mice were genotyped by SNP analysis. To identify tumor intrinsic factors controlling the response to chemotherapy, we transplanted 125 tumors collected from the backcross mice into singenic F1-C57/FVB mice to remove variability coming from the host compartments. Each tumor was transplanted into two F1 reciplent mice; each one was treated with Doxorubicin or Docetaxel, and we studied tumor response to treatment. Linkage analysis permits us to identify QTL (Quantitative Trait Loci) controlling susceptibility to mammary cancer and evolution of the disease in the backcross population, and the specific intrinsic QTL associated with different chemotherapy responses in the F1 mice. Moreover, we are studying molecular and signalling pathways that control chemotherapy responses and the QTL associated with them. The identification of breast cancer susceptibility genes and their pathways associated with different response to chemotherapy will be important for the prediction of human breast cancer evolution during therapy, and to learn about the mechanisms involved in resistance to chemotherapy, thus it would help to develop new preventivo and therapeutic strategies.
DescripciónResumen del trabajo presentado a la EACR-OECI Conference: "Precision Medicine for Cancer", celebrada en Neumünster Abbey (Luxemburgo) del 1 al 4 de marzo de 2015.-- et al.
Aparece en las colecciones: (IBMCC) Comunicaciones congresos
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