Researchers Review TRK Cancer Mutations As Targets In New Clinical Trials

Researchers Review TRK Cancer Mutations As Targets In New Clinical Trials

shutterstock_201062513A recent study published in the journal Cancer Discovery reviewed several clinical trials that are using drugs targeting the TRK gene for the treatment of different types of cancer, including colorectal cancer.

In 1982 this gene was shown to be responsible for a low percentage of colon cancers. In the two last years, the advance in research technology allowed genetic sequencing of tumor samples, revealing several fusions of the TRK family of genes in 11 different types of tumor.

“We didn’t initially discover the gene. But now technology lets us find the gene in actual patient samples and drugs are available to target these gene rearrangements, making it possible to treat TRK cancers in clinical trials in ways we only dreamed of thirty-two years ago,” Robert C. Doebele, MD, PhD, investigator at the CU Cancer Center and associate professor of Medical Oncology at the CU School of Medicine said in a news release.

There are several genes that belong to the TRK family, including NTRK1, NTRK2 and NTRK3, which play an essential role in the development of the nervous system. After birth, these genes lose their importance, and as such, they are silenced in several tissues.

However, some tumors have the capacity to awaken TRK genes, upon fusion with other genes, initiating a signaling cascade that allows cells to proliferate and become immortal, eventually leading to cancer.

“What we’re finding is that while TRK fusions may not be the major cause in any single, major cancer, it’s the cause of small percentages of many cancer types,” Dr. Doebele added.

In this recent study, researchers note that 1.5% of colorectal cancers, 3.3% of lung cancers and 12.3% of thyroid cancers present NTRK fusions.

“These numbers add up,” Dr. Doebele noted.

Ten years ago there were no drugs able to specifically target NTRK fusions and similar types of genetic rearrangements. However, now there is an entire class of drugs, in particular tyrosine kinase inhibitors, that have the capacity to turn off these genetic abnormalities. Once such example is the FDA approved drug crizotinib, which targets ALK and ROS1 fusions in lung cancer. Furthermore, investigational drugs such as RXDX-101, TSR-011, LOXO-101 and PLX-7486 specifically target TRK fusions.

“A lot of doctors in academia or community hospitals are ordering next-generation sequencing panels for their patients. If it turns out that patients’ tumors have TRK alterations, I want their doctors to know that there are treatment options available via clinical trials,” Dr. Doebele concluded.

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