Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma.

ABSTRACT: The progression of cancer is an evolutionary process that is challenging to assess between sampling timepoints. However, investigation of cancer evolution over specific time periods is crucial to the elucidation of key events such as the acquisition of therapeutic resistance and subsequent fatal metastatic spread of therapy-resistant cell populations. Here we apply mutational signature analyses within clinically annotated cancer chronograms to detect and describe the shifting mutational processes caused by both endogenous (e.g. mutator gene mutation) and exogenous (e.g. mutagenic therapeutics) factors between tumor sampling timepoints. In one patient, we find that cisplatin therapy can introduce mutations that confer genetic resistance to subsequent targeted therapy with Erlotinib. In anot

SUBMITTER: Fisk JN 

PROVIDER: S-EPMC8702484 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature