Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

Cancers (Basel). 2021 Feb 15;13(4):804. doi: 10.3390/cancers13040804.


Due to groundbreaking developments and continuous progress, the treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has become an exciting, but increasingly challenging task. This applies, in particular, to the subgroup of NSCLC with oncogenic driver alterations. While the treatment of epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged NSCLC with various tyrosine kinase inhibitors (TKIs) is well-established, new targets have been identified in the last few years and new TKIs introduced in clinical practice. Even for KRAS mutations, considered for a long time as an "un-targetable" alteration, promising new drugs are emerging. The detection and in-depth molecular analysis of resistance mechanisms has further fueled the development of new therapeutic strategies. The objective of this review is to give a comprehensive overview on the current landscape of targetable oncogenic alterations in NSCLC.

Keywords: ALK gene rearrangements; BRAF mutations; EGFR exon 20 insertions; EGFR mutation; HER2 alterations; KRAS G12C inhibitors; KRAS mutations; MET alterations; NSCLC; NTRK gene fusions; RET gene rearrangements; ROS1 gene rearrangements; oncogenic alterations; targeted therapy.

Publication types

  • Review