Targeting the Epigenetic Regulator MLL3 Mutations in Breast Cancer
Abstract
The research proposed here will directly address two overarching challenges facing breast cancer treatment: (1) Identify what drives breast cancer growth; determine how to stop it; and (2) revolutionize treatment regimens by replacing interventions that have life-threatening toxicities with ones that are safe and effective. The cancer genome project, a global effort to categorize genetic alterations in human cancers, has provided great potential to develop novel targeted cancer therapies and tailor these therapies precisely to specific patients who will have best therapeutic benefit. However, to fulfill such potential, we have to identify and understand which mutations functionally contribute to the malignant phenotype of the cancer cells. Here, we will focus on a highly promising candidate breast cancer gene called MLL3 that has recently been identified by the human cancer genome project. MLL3 is one of the most frequently mutated genes in breast cancer. It is altered in more than 25% of breast cancer. Interestingly, this gene is mutated in all major subtypes of breast cancer. However, whether it is indeed functionally involved breast cancer development remains unclear, and no therapeutic agent is available for targeting cancers harboring the MLL3 mutations. Part of the problem is that current approaches for generating tumor models for understanding cancer gene function and for preclinical drug studies are time-consuming, inefficient, and costly. To address this issue, we have developed a new technology for generating personalized tumor models that carry mutations found in human patients. Using these novel and efficient models, we will decipher whether MLL3 mutations drive breast cancer development and whether these mutations may affect the efficacy of targeted therapies that are currently being tested in clinical trials. Furthermore, we will elucidate the mechanisms mediating the action of MLL3 mutations and apply these understandings to develop therapeutic strategies for targeting cancer cells harboring MLL3 mutations. Successful outcomes of this study will pave the way for clinical development of therapeutic agents that target breast cancer carrying alterations of this novel cancer gene. In addition, the technology optimized through this study will be highly valuable for investigating other novel breast cancer mutations for systematically identifying cancer targets that can be tailored for personalized medicine.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610311
Entities
People
- Wenjun Guo
Organizations
- Albert Einstein College of Medicine
- United States Army