Predictive Biomarkers for Novel and Established Therapies of Small Cell Lung Cancer
Abstract
The goal of this proposal is to test how we can best use the genetic make-up of small cell lung cancer (SCLC) to identify patients who are most likely to benefit from treatment with a new type of drugs called PARP inhibitor. PARP inhibitors belong to a class of drugs that limit the ability of cancer cells to repair damage induced by standard treatment like chemotherapy or radiation. These drugs can also be effective in tumor cells with deficient genetic make-up. Because these drugs do not work in all patients, it is important to find a reliable way to select patients who are most likely to benefit. Laboratory work conducted by our group at Emory University identified a group of genes that are different between cancer cells that respond and do not respond to PARP inhibitor in the laboratory. We expect that these genes are also likely to identify patients likely to benefit from PARP inhibitor. In addition, a separate test called Homologous Recombination Deficiency (HRD score) has been shown to also predict benefit of PARP inhibitor in patients with ovarian and breast cancer. This HRD score is now approved by the Food and Drug Administration for this purpose. However, the best way to use the test varies from one type of cancer to another. Because this HRD score has not been tested in SCLC, we currently do not know how best to use it to select SCLC patients for treatment. Our goal therefore is to use tumor samples obtained from SCLC patients who were enrolled in a clinical trial of PARP inhibitor to further refine these two laboratory tests. The high rate of tobacco use and exposure to environmental pollutants put active military members and beneficiaries at a high risk for lung cancer. Because the association between tobacco and lung cancer is strongest for the subset of patients with SCLC lung cancer, our proposal is very important to active duty military members, Veterans, and their relatives. Our proposal will also address several areas of emphasis proposed for study by the Lung Cancer Research Program such as identifying new strategies for prevention and treatment of lung cancer and also the emphasis on developing special tests that can foretell patients that will respond or not respond to a particular treatment. Important steps that will advance the development of this laboratory tests as part of the standard management for SCLC in the near future include (1) showing significant differences between patients who differ in the gene expression and HRD score using the result of study that has already been completed and (2) establishing the most reliable way to use these tests to select patients for treatment (also referred to as predictive biomarkers). The results of our proposed study will have great impact on the care of lung cancer patients, especially military beneficiaries who are more likely to suffer from this condition. The results will be useful to decide whether or not patients should be treated with PARP inhibitors, should the result of the clinical trial lead to the approval of this drug in the future. In addition, if the result of the clinical trial turns out negative, these biomarkers may allow us to gain a better understanding of why the trial failed, thereby giving us some guidance on a better way to design other studies of PARP inhibitor in the future. We will be able to complete the work proposed in this study within 2 years. It is also expected that a positive result from this study will contribute to a greater likelihood of success of PARP inhibitors in SCLC, thereby making a new drug available for SCLC in the year.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610108
Entities
People
- Taofeek Owonikoko
Organizations
- Emory University
- United States Army