Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution
Abstract
Scientific Objective: The goal of the proposed research is to develop a prognostic test that could predict if a lung cancer is likely to metastasize or not. This knowledge is important because it would change the management and treatment of lung cancer patients. In order to develop this test, we will take advantage of recent progress in understanding how tumors evolve. We will compare the pattern of gene mutations in tumors that have and have not metastasized in order to develop a "prognostic score" that will correlate with the tumor s aggressiveness (or lack thereof). Clinical Application: When a lung tumor is detected, clinical staging with imaging is currently used to determine how advanced the tumor is. If the tumor is deemed to be "early stage," i.e., there is no evidence of spread beyond the lungs, the tumor is usually removed by surgery. If the imaging assessment was right and the tumor had truly not yet metastasized, the patient would be totally cured at that point. However, the imaging assessment is frequently wrong. In almost half of "early stage" cases, recurrent tumors usually appear within months or several years after the original lung tumor is removed. We aim to develop a new test, based on analyzing gene mutations in the tumor after it is removed from the patient, that will discern the likelihood that the tumor had already metastasized. If the test were to indicate metastasis had occurred, more aggressive treatment and/or more frequent follow-ups would be recommended. If the test showed that the tumor had not metastasized, no further treatment would be necessary and less frequent follow-ups would be appropriate. Potential Benefits: This test would benefit patients in two important ways: (1) Patients whose tumor had already metastasized could be treated more aggressively, e.g., with chemotherapy, that could help prolong their lives. (2) Patients whose tumor had not metastasized would be spared the side effects of therapy. Potential Risks: An important feature of the proposed test is that the test itself would cause no risk to the patient. There are, however, potential risks regarding treatment decisions that are made based on the test results. For example, if the test were to suggest that the tumor had metastasized when actually it had not, the patient could receive unnecessary chemotherapy. Likewise, incorrectly assuming the absence of metastasis could cause a patient to go untreated when aggressive treatment would have been the preferred course of action. Projected Time to Achieve Clinically Relevant Outcome: It is our goal to make sure that the test results are absolutely accurate. Optimization of the test will require carefully planned clinical trials. Once these trials are complete, the test will be available for day-to-day use in clinics in several years. Contribution of This Study to Advancing the Field of Lung Cancer Research: Inherent in the work proposed in this grant application is the possibility that important clues to lung tumor growth and progression may be uncovered as a result. Since we will determine the DNA sequence of large numbers of genes in individual tumor cells isolated from numerous lung tumors, considerable knowledge regarding the types of mutations important for lung tumor progression may be discovered. This knowledge could result in the design of novel targeted therapies with better tumor killing and fewer side effects than currently available therapy. Importantly, this potential benefit would be present regardless of whether the test is deemed to be feasible. Summary: We propose to investigate the feasibility of a test that would result in vastly improved clinical management of lung cancer. This test would be most beneficial to patients whose lung tumors are considered "early stage" using currently available clinical methods. In addition, it is possible that valuable information regarding lung tumor growth and progression will be uncove
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510243
Entities
People
- Edward Patz
Organizations
- Duke University
- United States Army