Abstract Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, and therapeutic management has advanced to identify various critical oncogenic mutations that promote lung cancer tumorigenesis. Subsequent studies have developed targeted therapies against these oncogenes in the hope of personalized treatment based on the tumor’s molecular genomics. This review presents a comprehensive review of the biology, new therapeutic interventions, and resistance patterns of two well-defined subgroups, tumors with KRAS and MET alterations. We also discuss the status of molecular testing practices for these two key oncogenic drivers, considering the progressive introduction of next-generation sequencing (NGS) and RNA sequencing in regular clinical practice.

Conclusion As genomic understanding of cancer improves, the knowledge regarding lung cancer have created so many different categories, that lung cancer is no longer a single disease, but a group of heterogenous neoplastic disorders that differ slightly or even drastically in their genetic makeup. During the last decade, the revolution of targeted therapy and immunotherapy have increased considerably the number of clinical trials and therapies approved for specific types of driver-mutated lung cancer. The availability of a targeted approach to KRAS is just a few years away from current therapy. Some TKIs have improved the survival of patients harboring MET alterations, however, a wide array of clinical trials are running, with promising results in the near future.

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