TP53 mutant cell lines selected for resistance to MDM2 inhibitors retain growth inhibition by MAPK pathway inhibitors but a reduced apoptotic response.

ABSTRACT:

Background

Emergence of resistance to molecular targeted therapy constitutes a limitation to clinical benefits in cancer treatment. Cross-resistance commonly happens with chemotherapeutic agents but might not with targeted agents.

Methods

In the current study, TP53 wild-type cell lines with druggable MAPK pathway mutations [BRAF ^V600E (WM35) or NRAS ^Q61K (SJSA-1)] were compared with their TP53 mutant sublines (WM35-R, SN40R2) derived by selection for resistance to MDM2/p53 binding antagonists.

Results

The continued presence of the druggable MAPK pathway targets in the TP53 mutant (TP53 ^MUT) WM35-R and SN40R2 cells was confirmed. Trametinib and vemurafenib were tested on the paired WM35/WM35-R a

SUBMITTER: Wu CE 

PROVIDER: S-EPMC6407233 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature