Journal article
Narrative review: mesenchymal-epithelial transition inhibitors—meeting their target
Translational lung cancer research, Vol.10(1), pp.462-474
01/01/2021
DOI: 10.21037/tlcr-20-588
PMCID: PMC7867750
PMID: 33569327
Abstract
Genetic alterations in mesenchymal-epithelial transition (MET) are commonly found in solid tumors, especially in non-small cell lung cancer (NSCLC). However, agents targeting MET have not progressed until recently. Advancements in our understanding of the role of various
MET
aberrations in carcinogenesis have allowed MET-directed therapy to find its way to clinic use. Of all
MET
alterations,
MET
exon 14 skipping (
METex14
skip
+
or
MET
∆
14
), stands out as a true oncogenic driver. Recently, MET tyrosine kinase inhibitors (TKI) targeting
METex14
skipping were able to demonstrate significant improvement in clinical outcomes including response rate and progression free survival. Of these, capmatinib was granted accelerated approval by the FDA in May 2020 for patients with advanced NSCLC harboring
METex14
skip alterations. Tepotinib, another TKI, has shown significant activity in a phase II trial and received breakthrough therapy designation from the FDA in September 2019.
MET
amplification (
MET
Amp
) and overexpression are usually a late phenomenon in tumorigenesis and aggravate malignant properties of transformed cells. Capmatinib and savolitinib have shown activity in patients with NSCLC with high levels of
MET
Amp
. Several other agents are being developed and under evaluation in clinical trials involving multiple tumor types. In addition to TKIs, MET overexpression is also an appealing target for development of antibody conjugated chemotherapy. Understanding the mechanisms of resistance to MET TKIs and alterations in anti-tumor immunity through MET inhibition are clinically relevant areas that need further exploration.
Details
- Title: Subtitle
- Narrative review: mesenchymal-epithelial transition inhibitors—meeting their target
- Creators
- Danish Safi - University of IowaTaher Abu Hejleh - University of IowaMuhammad Furqan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Translational lung cancer research, Vol.10(1), pp.462-474
- DOI
- 10.21037/tlcr-20-588
- PMID
- 33569327
- PMCID
- PMC7867750
- NLM abbreviation
- Transl Lung Cancer Res
- ISSN
- 2218-6751
- eISSN
- 2226-4477
- Publisher
- AME Publishing Company
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359769202771
Metrics
6 Record Views