Doctors and researchers have known about a biomarker known as MTAP deletion for many years. But now they’re learning what role this gene plays in lung cancer and other tumors. Long ago, this genetic alteration was thought to be just collateral damage in tumors, but now researchers are uncovering its influence on tumors. It turns out there are some advantages for a tumor to have this MTAP gene loss. This new understanding means new medications can likely be developed to open a new weak point in the cancer to allow for targeted therapy.
Looking Closer at Biomarkers and MTAP Deletion
The “specific biomarkers” in the cells of a tumor can be used to determine the best course of treatment for a lung cancer patient. Methylthioadenosine phosphorylase (MTAP) deficiency, also known as MTAP deletion, is a genetic alteration in lung cancer that’s independent of other established biomarkers. MTAP is not exclusive to a more established genetic alteration. Doctors can see MTAP loss in patients with EGFR mutation or KRAS mutations or in those that these genes are wild type.
What makes MTAP deletion so unique?
Deletion of MTAP is associated with multiple tumors such as mesothelioma, bladder urothelial cancer, pancreatic cancer, and lung cancer among others. Recent studies show that MTAP loss occurs in 13% of non-small cell lung cancer (NSCLC).
According to Dr. Rodon, knowing MTAPs’ metabolic vulnerabilities, some chemotherapies would be more productive in this genetic alteration. Drugs that inhibit metabolic activity could be developed into targeted therapy for MTAP-deficient tumors.
“This new generation of drugs, specifically targeting MTAP could also be a great therapeutic tool. There are so many points of view, so many ways of using this. In the next years, I think research will bloom in this field of targeting MTAP, using it as a prognostic factor, as a predictive factor of chemo, and as a selection marker for this new generation of drugs.”
– Jordi Rodon Ahnert, MD, PhD
What is happening with clinical trials for MTAP deletion?
Only recently recognizing its importance, researchers are testing for this genetic alteration and are developing drugs to target MTAP deletion. There was a first generation of trials with all drugs and now there is a second generation of medications that look really promising. In the early days, these clinical trials are typically located in big academic centers where they are specializing in all the complexities of new medications.
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