# name
ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins

# metadata.dc.description.abstract[].value
Breast cancer is the most frequent type of cancer and the major cause of mortality in women. The rapid development of various therapeutic options has led to the improvement of treatment outcomes; nevertheless, one-third of estrogen receptor (ER)-positive patients relapse due to cancer cell acquired resistance. Here, we use dynamic BH3 profiling (DBP), a functional predictive assay that measures net changes in apoptotic priming, to find new effective treatments for ER+ breast cancer. We observed anti-apoptotic adaptations upon treatment that pointed to metronomic therapeutic combinations to enhance cytotoxicity and avoid resistance. Indeed, we found that the anti-apoptotic proteins BCL-xL and MCL-1 are crucial for ER+ breast cancer cells resistance to therapy, as they exert a dual inhibition of the pro-apoptotic protein BIM and compensate for each other. In addition, we identified the AKT inhibitor ipatasertib and two BH3 mimetics targeting these anti-apoptotic proteins, S63845 and A-1331852, as new potential therapies for this type of cancer. Therefore, we postulate the sequential inhibition of both proteins using BH3 mimetics as a new treatment option for refractory and relapsed ER+ breast cancer tumors.

# metadata.dc.description.sponsorship[].value
This research was funded by National Science Foundation grants PHY 1545832 (to R.A.), PHY 1545839 (to A. L. and N.W.) and 1545853 (to M.S.), the Stand Up to Cancer Foundation, and Stand Up to Cancer Foundation/The V Foundation Convergence Scholar Awards to J.G.T.Z. (D2015-039), J.M. (D2015-037). J.M. acknowledges support from the Ramon y Cajal Programme, Ministerio de Economia y Competitividad (RYC-2015-18357) and the Spanish National Plan “Retos Investigacion” I + D + i (RTI2018-094533-A-I00) from Ministerio de Ciencia, Innovación y Universidades. J.M. and C.A. acknowledge the CELLEX foundation. The Nanobioengineering Group has support from the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 1079). The authors acknowledge the support of CERCA Programme/Generalitat de Catalunya.

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Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

# metadata.dc.title[].value
ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins