Role of c-Myc in lung cancer: Progress, challenges, and prospects

Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite the recent advances in cancer therapies, the 5-year survival of non-small cell lung cancer (NSCLC) patients hovers around 20%. Inherent and acquired resistance to therapies (including radiation, chemotherapies, targeted drugs, and combination therapies) has become a significant obstacle in the successful treatment of NSCLC. c-Myc, one of the critical oncoproteins, has been shown to be heavily associated with the malignant cancer phenotype, including rapid proliferation, metastasis, and chemoresistance across multiple cancer types. The c-Myc proto-oncogene is amplified in small cell lung cancers (SCLCs) and overexpressed in over 50% of NSCLCs. c-Myc is known to actively regulate the transcription of cancer stemness genes that are recognized as major contributors to tumor progression and therapeutic resistance; thus, targeting c-Myc either directly or indirectly in mitigation of the cancer stemness phenotype becomes a promising approach for development of a new strategy against drug resistant lung cancers. This review will summarize what is currently known about the mechanisms underlying c-Myc regulation of cancer stemness and its involvement in drug resistance and offer an overview on the current progress and future prospects in therapeutically targeting c-Myc in both SCLC and NSCLC.