Raphael E. Pollock MD, PhD - Professor and Director, Division of Surgical Oncology
Vice Chairman for Clinical Affairs, Department of Surgery
Surgeon in Chief, James Comprehensive Cancer Center
Surgeon in Chief, The Ohio State University Health System
Physician, FGP-Surgical Oncology
1. The role of HDAC inhibitors in augmenting chemosensitivity of complex karyotype sarcoma. Histone deactylase inhibitors are a class of drugs that may help increase the effectiveness of standard chemotherapy agents in many forms of cancer, including sarcoma. This increase in effectiveness is not always seen, and when not achieved it may be because an additional process, termed autophagy, is induced by the HDAC inhibitors. In this context, autophagy helps tumor cells survive the effects of chemotherapy by recycling key cellular components needed to sustain growth. We hope to better understand the underlying biology of this process and move forward with clinical trials to down-regulate autophagy processes.
2. Molecular determinants underlying desmoid tumor recurrence. Desmoid tumors are rare lesions that can be very locally invasive and locally recurrent, even after successful treatment. We have identified a specific mutation in the gene that controls desmoid over-production of beta-catenin, a protein that is the most commonly over-produced protein in desmoid tumors. Beta-catenin participates in a signaling pathway that triggers desmoid tumor cell growth. The gene mutation we have identified is associated with much higher rates of recurrence, and we are now interested in learning if other Beta-catenin-associated proteins might serve as therapeutic targets to decrease rates of desmoid tumor recurrence.
3. The well differentiated:dedifferentiated liposarcoma dichotomy. Liposarcoma is a family of sarcoma subtypes. Two prominent members of this cohort, well differentiated and dedifferentiated liposarcoma, are frequently seen within the same tumor or sometimes within the same patient at different times. Dedifferentiated liposarcoma can disseminate to other parts of the body whereas well differentiated liposarcoma cannot. We are discovering that the molecular biology of these two co-exisiting tumors is very different, and may be exploitable and lead to new molecular-based therapeutics for this sarcoma cluster of diseases.