P76.43 Co-occurring genomic alterations and treatment outcomes in patients with EGFR exon 20 insertion positive NSCLC

Coexpression of TP53, BIM, and PTEN Enhances the Therapeutic Efficacy of Non-Small-Cell Lung Cancer

“…In NSCLC, it is noteworthy that some genomic alterations in oncogenic genes and tumor suppressor genes could co-occur. − Taking NCI-H1299 cancer cells as an example, p53 works on multiple signaling pathways, including cell proliferation, cell apoptosis, DNA repair, and cell senescence. In NCI-H1299 cells, p53 expression is often transcriptionally closed .…”

“…For example, as one of the pro-apoptotic proteins of the BCL-2 family, BCL2L11 (also called BIM) plays a critical role in regulating the intrinsic apoptotic pathway for programmed cell death . Many studies have shown that BIM is a key apoptotic effector in tyrosine kinase inhibitor (TKI)-induced killing of EGFR mutant NSCLC , and BIM gene deletion can affect the diagnosis and treatment of advanced NSCLC. , In NSCLC, these genes might be combined to regulate different signaling pathways as a whole gene network for carcinogenesis and progression, which further adds the complexity and difficulty of NSCLC treatment with single-gene target therapies. − Although single-gene target therapies may be effective in some specific cases in the short term, they will be limited in the long run due to drug resistance. Resistance to anticancer therapies is primarily driven by the presence of more than one target (primary resistance) and adaptation to treatment selection pressure (secondary resistance).…”