Fig. 3.

Relevance of timing on treatment response to CDK4/6i-based combination therapy. First-line therapy with platinum-based chemotherapy (CTX) triggers resistance and impedes response to CDKi (upper part). Addition of EGFR-blocking antibody cetuximab can partially suspend resistance. However, in case of first-line (middle part) or simultaneous (lower part) CDKi, developing resistance can be prevented in TP53-mutated cells, resulting in effective tumor growth control [33, 34]. ATM, ataxia telangiectasia mutated; CDK, cyclin-dependent kinase; pRNA pol II, phospho RNA polymerase II; SE-associated, super-enhancer-associated. Response includes objective response rate and complete response rate. Created with BioRender.com