2014 Kirwin-Hinton Family Scholar
Michael Goldberg, PhD
Dana-Farber Cancer Institute
Targeted disruption of ovarian tumor stroma to enhance penetration of therapies and lymphocytes
The majority of cancer therapies attempt to kill tumor cells using drugs that are often toxic. Many patients relapse because residual cells can establish new drug-resistant tumors. Unlike traditional therapies, the immune system can adapt to the evolving tumor. In fact, immune cell infiltration into tumors is the best known predictor of patient outcomes. Frustratingly, tumors secrete a physical barrier to prevent the penetration of immune cells and other medicines. Accordingly, Dr. Goldberg is developing nanoparticles that break down this obstruction (like a molecular battering ram through a fortress wall) to facilitate immune cell and drug penetration, thereby improving survival outcomes.
Pradeep Raghavan, PhD
University of Texas MD Anderson Cancer Center
Unraveling the oncogenic effects of amplified miRNAs in High Grade Serous Epithelial Ovarian Cancer
Cancer cells are abnormal partly by having increased copies of certain genes (DNA copy number aberrations), which is an important hallmark of high-grade serous ovarian cancer. Non-protein coding genes such as microRNAs have recently been implicated in both tumor initiation and progression and represent understudied potential drivers of cancer behavior. Dr. Raghavan‘s preliminary data shows that microRNA miR551b is amplified in approximately 35% of ovarian cancer patients. Initial evidence suggests that miR551b operates by hijacking the tumor suppressor pathways which block the growth and development of cancer. In this project, he will identify the mechanisms underlying how miR551b promotes tumor growth and metastasis as well as therapeutic opportunities.
2014 Skacel Family Scholar
Capucine Van Rechem, PhD
Massachusetts General Hospital
Copy Gain and Resistance: Uncovering Roles for Epigenetic Regulation in Ovarian Cancer
A major issue in the treatment of ovarian cancer is the development of resistance to standard chemotherapy. Such drug resistance has been linked to the gain of a specific genomic region, 1q12-1q21. Dr. Van Rechem recently demonstrated that the amplification of a regulator of genome organization, KDM4A, is associated with a faster time to death in ovarian cancer patients and also caused 1q21 gain. Therefore, the project will investigate the function of KDM4A in promoting drug resistance in ovarian cancer. These studies will bridge molecular mechanisms and clinical relationships so that disease mechanisms and possible treatment options for ovarian cancer patients can be identified.