TY - JOUR
T1 - Current and future treatment options for MET exon 14 skipping alterations in non-small cell lung cancer
AU - Hong, Lingzhi
AU - Zhang, Jianjun
AU - Heymach, John V.
AU - Le, Xiuning
N1 - Funding Information:
Zhang reports research funding from Merck and Johnson and Johnson, personal fees from AstraZeneca, Bristol-Myers Squibb, GenePlus-Beijing Institute, Innovent outside the submitted work. Heymach receives advisory/consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Kairos Venture Investments, BrightPath Therapeutics, Hengrui Therapeutics, Eli Lilly, EMD Serono, and Foundation One Medicine, Spectrum, AstraZeneca, and research Funding from NIH/NCI, American Cancer Society, and Checkmate Pharmaceuticals, and AstraZeneca, Spectrum; and Royalties and Patents from Spectrum. Le receives consultant and advisory fee from Eli Lilly, AstraZeneca, EMD Serono, and research funds from Eli Lilly, Boehringer Ingelheim, and Spectrum Pharmaceuticals. All outside of the submitted work.
Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Lingzhi Hong is supported by MD Anderson Visiting Scholar Program, the key project from the Medical Science and Technology Department Foundation, Nanjing Department of Health, Nanjing, China (Grant No: ZKX15029). Jianjun Zhang is supported by MD Anderson Physician Scientist Award, NIH R01, AACR Johnson and Johnson Innovative Cancer Research Award, Khalifa Scholarship, and Conquer Cancer Foundation. Xiuning Le is supported by Calabresi Paul Award at MDACC (K12/NIH), Rexanna Foundation, Khalifa Scholarship, and Conquer Cancer Foundation.
Publisher Copyright:
© The Author(s), 2021.
PY - 2021
Y1 - 2021
N2 - It has been over three decades since the hepatocyte growth factor (HGF) ligand and its receptor MET proto-oncogene (MET) pathway was established as promoting cancer growth and metastasis. MET exon 14 skipping (METex14) alterations occur in 3–4% of all non-small cell lung cancer (NSCLC) patients, typically in elderly patients (older than 70 years), and result in constitutive activation of the MET receptor by altering a region required for receptor degradation. Multi-kinase inhibitor of MET, such as crizotinib, and more recently selective MET inhibitors, such as capmatinib and tepotinib, have demonstrated clinical efficacy and safety in METex14 NSCLC patients in clinical trials. These results have led to the approval of MET inhibitors by regulatory agencies across the globe. The success also fueled the excitement of further development of therapeutic strategies to target METex14 in lung cancers. This article provides an overview of the clinical development program targeting METex14 in NSCLC, including small molecular tyrosine kinase inhibitors and anti-MET antibodies. Furthermore, combination therapy immune checkpoint inhibitors or other targeted therapies are also under development in various patient populations, with acquired resistance immune or targeted therapy. Clinical trials in different development stages are ongoing and more drugs targeted to c-MET will be available for NSCLC patients with METex14 skipping mutations in the future.
AB - It has been over three decades since the hepatocyte growth factor (HGF) ligand and its receptor MET proto-oncogene (MET) pathway was established as promoting cancer growth and metastasis. MET exon 14 skipping (METex14) alterations occur in 3–4% of all non-small cell lung cancer (NSCLC) patients, typically in elderly patients (older than 70 years), and result in constitutive activation of the MET receptor by altering a region required for receptor degradation. Multi-kinase inhibitor of MET, such as crizotinib, and more recently selective MET inhibitors, such as capmatinib and tepotinib, have demonstrated clinical efficacy and safety in METex14 NSCLC patients in clinical trials. These results have led to the approval of MET inhibitors by regulatory agencies across the globe. The success also fueled the excitement of further development of therapeutic strategies to target METex14 in lung cancers. This article provides an overview of the clinical development program targeting METex14 in NSCLC, including small molecular tyrosine kinase inhibitors and anti-MET antibodies. Furthermore, combination therapy immune checkpoint inhibitors or other targeted therapies are also under development in various patient populations, with acquired resistance immune or targeted therapy. Clinical trials in different development stages are ongoing and more drugs targeted to c-MET will be available for NSCLC patients with METex14 skipping mutations in the future.
KW - MET exon 14 skipping
KW - antibody
KW - hepatocyte growth factor
KW - non-small cell lung cancer
KW - tyrosine kinase inhibitor
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U2 - 10.1177/1758835921992976
DO - 10.1177/1758835921992976
M3 - Review article
C2 - 33643443
AN - SCOPUS:85101048506
SN - 1758-8340
VL - 13
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
ER -