Editorial: Challenges and opportunities of TKIs in the treatment of NSCLC patients with uncommon mutations

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Chunxia Su, Tongji University School of Medicine

Shi-Yong Sun, Emory University

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This study was supported by the National Natural Science Foundation of China (grant numbers: 81874036, 82072568), the Science and Technology Commission of Shanghai Municipality (grant number: 19411971100) and the Shanghai Shenkang Hospital Development Center (grant number: SHDC12020110).

Abstract

Substantial advances have been made in our understanding of the molecular biology of cancer, leading to profound progression in the fields of diagnosis and treatment of non-small cell lung cancer (NSCLC). More recently, many uncommon mutations are gaining attention in NSCLC, including epidermal growth factor receptor exon 20 insertion (EGFR 20ins), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), rearranged during transfection (RET), v-Raf murine sarcoma viral oncogene homolog B (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), and others (1). Pharmaceutical agents developed to target classical driver mutations detected in NSCLC patients have provided profound and durable responses compared with conventional chemotherapy. This paradigm shift can also be seen in the realm of uncommon mutations. Ongoing studies and clinical trials of tyrosine kinase inhibitors (TKIs) for uncommon targets are gaining insights into possible treatment options to enable long-term survival of patients. Since immunotherapy serves as the backbone treatment in mutation-negative populations, the efficacy of immunotherapy or immunotherapy-based combinations has also been evaluated in patients harboring uncommon targets. Furthermore, other novel therapies and platforms have been developed and tested to provide more possibilities and options for these patients.

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