Lung cancer is the leading cause of cancer death in the US and worldwide with 15-18% cure rate. Thus, prevention is a critical strategy to decrease lung cancer deaths. Tobacco smoking causes the large majority of lung cancer and smoking cessation is the best intervention in smokers; however, the risk of lung cancer in former smokers remains high. The administration of drugs or natural products to prevent cancer is called chemoprevention. Unfortunately, currently, no drug, natural product or vitamin has been shown to decrease lung cancer incidence in humans.
The prostacyclin analog, iloprost, prevents lung cancer in mice exposed to tobacco smoke, as well as other chemicals. Therefore, we performed an early phase clinical trial of iloprost in humans. Iloprost improved airway changes that lead to lung cancer in humans, but only in former, not current, smokers. 59% of former smokers given iloprost improved airway dysplasia compared to 29% given placebo. Our goal is to be able to identify those former smokers who will benefit from iloprost so as to treat the right patients with the right drug. We have developed a patient-derived epithelial progenitor cell culture that can lead to such a test, as it recapitulates the morphologic improvement in dysplasia. Preliminary data suggest that gene expression differs between iloprost responders and non-responders at baseline. If we can develop a biomarker to discriminate responders from non-responders, future clinical trials can be accelerated and if positive, iloprost chemoprevention can be targeted to the correct subset of former smokers.
Funded by the Kay Yow Cancer Fund
Funded by Papa John’s International, Inc.
Funded by The V Foundation Wine Celebration Vintner Grant
In honor of Ariene Cosentino
Funded by Papa John’s International
Recipient of the V Scholar PLUS Award, a third year of grant support for V Scholars who have made exceptional progress in year 1 and 2 of their original grant
The precision oncology approach to the treatment of cancer bases treatment decisions on the biology of an individual’s cancer, most often using genetic alterations or mutations to inform therapy. This approach has been successful in a few cancer types, including lung cancer, melanoma, and chronic myelogenous leukemia where oral targeted therapies have led to both improved patient outcomes and fewer side effects compared to standard chemotherapy. However, this approach has not yet realized its full potential in these or other cancer types. In this proposal we plan to study new cancer-causing gene mutations involving the NTRK1, NTRK2 and NTRK3 genes, which are found in numerous types of cancer. We have already demonstrated that tumor cells treated with targeted therapies against this gene family can kill cancer cells in the laboratory. We have also observed early and dramatic tumor shrinkage in patients with different tumor types that share mutations in these NTRK genes. This proposal will focus on determining additional mutations of NTRK genes that may respond to therapy. The proposal will also study how cancer cells become resistant to targeted therapies and develop new laboratory models of NTRK+ cancer to develop new therapies for these cancers.
Funded in Memory of Calvin Bradham
with support from Crown Imports
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