A new editorial paper was published in Oncotarget Volume 14 on May 26, 2023.

In their new editorial, researchers Mira Al Jaberi, Wolfgang Clough and Samir Dalia from Mercy Hospital discuss the MET gene.

Several alterations in the MET gene were identified as targetable oncogenic changes leading to non-small cell lung cancer (NSCLC).

These include genomic amplifications, exon 14 skipping mutations and fusion. 

Capmatinib has been considered as a first-line treatment for patients with NSCLC carrying a MET exon 14 skipping mutation since May 2020 by the US FDA.

A study newly published in early 2023 showed that crizotinib, a tyrosine kinase inhibitor, was also effective for MET fusions, which occur rarely in 0.2–0.3% of patients with lung cancer.

A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance. 

“A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance.” 

Several structurally different MET tyrosine kinase inhibitors (TKIs) have been developed or are under clinical evaluation.

TKIs are categorised into type I TKIs (type Ia: crizotinib; type Ib: savolitinib, capmatinib) and type II TKIs (cabozantinib, glesatinib, merestinib).

Combination therapy reduces resistance and enhances clinical outcomes.

“These clinical trials along with others will show us if other MET inhibitors or combination therapy may be better than the current standard of care.”

Article: Latest updates on MET targeted therapy for EXON 14 mutations in lung cancer

Source: Impact Journals LLC