Analysis of pulsed cisplatin signalling dynamics identifies effectors of resistance in lung adenocarcinoma.

ABSTRACT: The identification of clinically viable strategies for overcoming resistance to platinum chemotherapy in lung adenocarcinoma has previously been hampered by inappropriately tailored in vitro assays of drug response. Therefore, using a pulse model that closely mimics the in vivo pharmacokinetics of platinum therapy, we profiled cisplatin-induced signalling, DNA-damage and apoptotic responses across a panel of human lung adenocarcinoma cell lines. By coupling this data to real-time, single-cell imaging of cell cycle and apoptosis we provide a fine-grained stratification of response, where a P70S6K-mediated signalling axis promotes resistance on a TP53 wildtype or null background, but not a mutant TP53 background. This finding highlights the value of in vitro models that match t

SUBMITTER: Hastings JF 

PROVIDER: S-EPMC7282820 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature