Concomitant inactivation of the p53-and pRB Functional Pathways Predicts Resistance to DNA damaging drugs in Breast Cancer

Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance to DNA damaging drugs in breast cancer better than TP53 mutations alone. Further, we hypothesized that redundant pathway(s) may compensate for loss of p53-pathway signaling and that these are inactivated as well in resistant tumour cells.

Source: Molecular Oncology - May 7, 2015 Category: Cancer & Oncology Authors: Stian Knappskog, Elisabet O. Berge, Ranjan Chrisanthar, Stephanie Geisler, Vidar Staalesen, Beryl Leirvaag, Synnøve Yndestad, Elise de Faveri, Bård O. Karlsen, David Wedge, Lars A. Akslen, Peer K. Lilleng, Erik Løkkevik, Steinar Lundgren, Bjørn Østen Source Type: research