MET fusions are targetable genomic variants in the treatment of advanced malignancies

• Published in: Cell communication and signaling Vol. 22; no. 1; p. 20
• Main Authors: Sun, Dantong, Xing, Xiaoming, Wang, Yongjie, Hou, Helei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09-01-2024; BioMed Central; BMC
• Subjects: Brain cancer; c-Met protein; Cancer; Cancer therapies; Care and treatment; Cell Proliferation; Cholangiocarcinoma; Comorbidity; Complications and side effects; Development and progression; Diagnosis; Epidermal growth factor receptors; ErbB Receptors; Gene mutations; Genes; Genetic aspects; Genomics; Growth factors; Health aspects; Humans; Kinases; Lung cancer; Malignancy; Medical prognosis; MET fusions; MET-TKIs; Mutation; Mutation - genetics; Neoplasms - drug therapy; Neoplasms - genetics; Phosphorylation; Protein-tyrosine kinase; Proteins; Review; Risk factors; Signal transduction; Targeted therapy; Tumors; Tyrosine; China; MET-TKIs; MET fusions; Targeted therapy; Cancer
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-023-01454-0

Targeted therapy for malignancies has developed rapidly in recent years, benefiting patients harboring genetic mutations sensitive to relevant tyrosine kinase inhibitors (TKIs). With the development of targeted sequencing techniques, an increasing number of detectable genomic alterations in malignancies, including MET fusions, have been revealed. MET fusions, although rare among malignancies, might be functional driver genes that participate in activating downstream signaling pathways and promoting cell proliferation. Therefore, it is believed that MET fusions could be targetable genomic variants of MET, and inhibition of MET is considered an optionable therapeutic choice for patients harboring MET fusions. According to the summary presented in this review, we recommend MET-TKIs as suitable treatment agents for patients harboring primary MET fusions. For patients harboring acquired MET fusions after the development of resistance to TKIs targeting primary genomic alterations, such as sensitive EGFR mutations, treatment with a MET-TKI alone or in combination with TKIs targeting primary genomic alterations, such as EGFR-TKIs, is hypothesized to be a reasonable option for salvage treatment. In summary, MET fusions, despite their low incidence, should be taken into consideration when developing treatment strategies for cancer patients.