Robert Doebele, M.D., Ph.D.
We discovered this new cancer gene in one of my lung cancer patients at the University of Colorado, a young lung cancer patient who had never smoked. Unfortunately there were no clinical trials for this particular type of lung cancer at the time we discovered this gene. My goal is to develop a therapy for this specific type of lung cancer so that in the near future patients with this type of lung cancer will have better treatment options available that will hopefully lead to longer survival.
Genes make up the master blueprint of all living cells, including cancer cells. Mistakes, or mutations, in these genes cause some genes to be turned on all of the time making cells grow uncontrolled. In many cancers, a single mutated gene, called an oncogene, singlehandedly causes unchecked growth. Many of these oncogenes can be turned off by drugs called kinase inhibitors, which causes death of the cancer cell. Successful examples of this strategy include the treatment of EGFR mutation positive lung cancer with Tarceva (erlotinib) or treatment of ALK gene fusion positive lung cancer with Xalkori (crizotinib). A new class of oncogenes, called NTRK1 gene fusions, was recently discovered in a never smoking lung cancer patient by our laboratory. Additional cases of NTRK1 gene fusions were found in lung cancer cases and have been previously identifed in patients with colon cancer, glioblastoma, and thryoid cancer and a related gene fusion involving NTRK3 has been previously identified in secretory breast cancer, acute myeloid leukemia, and salivary gland tumors. The goal of this project is to prove that NTRK1 gene fusions control the fate of the cancer cell and that treatment with specific inhibitors of the NTRK1 gene will induce cancer cell death in laboratory experiments. Ultimately this project will identify inhibitors of the NTRK family of genes that can be used in a clinical trial for patients with lung cancer or other cancers that have mutated NTRK family members.
Why is this important?
This project will generate the critical data necessary to initiate a clinical trial of a targeted drug that can inhibit NTRK1 (and NTRK3) gene fusions in patients with lung cancer or other cancers that have evidence of this gene mutation. This project will also help define the best way to detect these gene mutations in tumor samples.
Who will benefit?
Patients with non-small cell lung cancer, especially those with lung adenocarcinoma who are never smokers are more likely to have an NTRK1 gene fusion. Other cancers that also have NTRK1, NTRK2, NTRK3 fusions genes include colon cancer, glioblastoma, thyroid cancer, secretory breast cancer, acute myeloid leukemia and others and may benefit from the development of drugs that can treat all of these abnormal genes.