Drosophila as a Screening Platform for Novel Lung Cancer Therapeutics
Abstract
Cancer has proven a difficult disease to address. Overall cancer mortality rates are improving slowly, yet it remains the second leading source of mortality for Americans. The largest source of cancer deaths is lung cancer, a collection of diseases of the adult lung. Our military has somewhat higher rates of smoking -- nearly a third of active duty personnel smoke -- putting our Service women and men at increased risk for lung cancer. Significant effort has gone into understanding the basis of lung cancer. For example, a key advance from the sequencing of the human genome is the ability to identify the DNA changes in a patient s tumor. This is important information as it helps oncologists match drug to patient. A key finding from sequencing efforts is that lung cancer patients typically have several genes that are mutated in a tumor. This complexity almost certainly contributes to the tumor s aggressiveness and makes fitting drugs to the disease more difficult. In addition to more traditional models, this proposal proposes to use the fruit fly Drosophila to take a different approach to lung cancer studies. Using sequence data from 15 individual patients, we will build "personalized fly models" that reflect the complexity of each patient s tumor. Once built, we will then use these "personalized flies" as tools to explore how the complex mutational profile affects tumor progression. In addition, we will use our models to assess how this complexity changes in response to a large panel of drugs. Our goal is to ask the question: How much complexity do we need to account for to create screening models that can identify the next generation of lung cancer therapeutics? The impact of this work on lung cancer therapeutics is potentially rapid, as the experiments include testing clinically relevant drugs. However, it is primarily designed to provide detailed information to improve our screening models. If successful, it will impact lung cancer drug discovery with effects several years down the road.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510111
Entities
People
- Ross Cagan
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army