The cMET gene, also known as MET, is a fundamental component within the human genome, carrying instructions for a protein that acts as a receptor on the surface of cells. This gene actively participates in numerous biological processes that govern cellular behavior. Understanding the cMET gene is a significant area of focus in scientific research, as its proper functioning is linked to maintaining cellular balance and health.
The cMET Gene’s Role in Healthy Cells
The cMET gene encodes the cMET receptor tyrosine kinase, a protein found on the outer membrane of various cell types. This receptor primarily binds to Hepatocyte Growth Factor (HGF), initiating a cascade of internal cellular signals.
This signaling pathway orchestrates several cellular activities, including controlled cell growth and proliferation. It also contributes to cell survival, protecting cells from programmed death, and facilitates cell migration, which is necessary for processes like tissue repair and regeneration. During embryonic development, cMET signaling is active, guiding the formation of various tissues and organs. In adults, its regulated activity is involved in wound healing, helping to close injuries and restore tissue integrity.
cMET’s Link to Disease Development
While cMET gene activity is beneficial when properly regulated, its dysregulation can contribute to various diseases, particularly cancer. Alterations in the cMET gene or its protein can lead to an overactive signaling pathway, promoting uncontrolled cellular behavior. This overactivity can result from gene amplification, where too many copies of the gene are present, or from specific mutations within the gene.
Overexpression of the cMET protein also contributes to this pathological state. An excessively active cMET pathway drives sustained cell growth and proliferation, enabling cancer cells to multiply unchecked. It also enhances cell survival, making cancer cells more resistant to therapies that induce cell death, and promotes metastasis, allowing cancer to spread aggressively to distant parts of the body. Alterations in cMET are commonly observed in several cancer types, including non-small cell lung cancer, gastric cancer, hepatocellular carcinoma (liver cancer), renal cell carcinoma (kidney cancer), and glioblastoma, a severe brain tumor.
Targeting cMET in Medical Treatment
Understanding how cMET dysregulation contributes to disease has paved the way for developing targeted therapies aimed at blocking its overactive pathway. These treatments, known as cMET inhibitors, are designed to interfere with the abnormal signaling that drives disease progression. They work by either preventing HGF from binding to the cMET receptor or by inhibiting the receptor’s internal signaling activity.
Two main categories of cMET-targeting drugs exist: small molecule inhibitors and monoclonal antibodies. Small molecule inhibitors, such as capmatinib or tepotinib, are typically taken orally and work by entering the cell to block the enzymatic activity of the cMET receptor. Monoclonal antibodies, like onartuzumab or tivantinib, are larger protein molecules administered intravenously; they function by binding to the cMET receptor on the cell surface, preventing HGF from activating it. While these treatments have shown promise in clinical trials, particularly in specific patient populations with cMET alterations, challenges such as drug resistance and identifying the most responsive patients continue to be areas of ongoing research.