Program Activities

The Molecular Therapeutics Research Program has been involved in:

• Monthly Program meetings
• Biweekly Phase I meetings
• Focus groups
  • Apoptosis > signal transduction > lipogenesis
• Sponsor seminars / grand rounds speakers
• Cancer Biology and Molecular Therapeutics graduate program
  • Research-in-progress, Journal clubs

Significant Accomplishments

• Demonstrated that combined docetaxel/gemcitabine followed by gemcitabine and radiotherapy improves treatment in locally advanced pancreatic cancer (Pipas et al., Ann Surg Oncol 12:995; 2005).
• Showed that the histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances gemcitabine-induced cell death in pancreatic cancer (Arnold et al., Clin Cancer Res 13:18; 2007).
• Completed a Phase I trial of the combination of cisplatin plus the checkpoint inhibitor UCN-01; identified a novel biomarker of cell cycle distribution that has been used to show cell cycle perturbation in serial tumor biopsies from patients receiving UCN-01 (Perez et al., Clin Cancer Res 12:7079; 2006).
• Defined distinct roles for p53-mediated transactivation and repression in preventing UCN-01-mediated abrogation of DNA damage-induced arrest at S and G2 cell cycle checkpoints (Levesque et al., Oncogene 24:3786; 2005).
• Developed a series of novel triterpenoids as anticancer drugs. The lead compound has entered Phase I clinical trials with initial responses observed in melanoma. (Numerous collaborative papers published; reviewed in Liby et al., Nat Rev Cancer 7:357; 2007)
• Demonstrated that the synthetic triterpenoid CDDO-Im inhibits fatty acid synthase expression and has antiproliferative and pro-apoptotic effects in human liposarcoma cells (Hughes et al., Cancer Investigation, in press).
• Demonstrated that the expression of the Spot 14 protein, a regulator of fatty acid synthesis, is an independent prognostic marker for recurrence of breast cancer independent of nodal involvement at diagnosis (Wells et al., Breast Cancer Res Treat 98:231; 2006).
• Discovered that conjugated linoleic acid, a dietary supplement that is considered a complementary medicine, inhibits expression of Spot 14 and fatty acid synthase, and suppresses the growth of breast cancer and liposarcoma cells.
• Demonstrated the frequent requirement for Hedgehog signaling in non-small cell lung cancer, including some lung cancer lines that have gain-of-function mutations downstream of the receptor and are resistant to current antagonists (Yuan et al., Oncogene 26:1046; 2007).
• Identified novel inhibitors of Smoothened that prevent signaling through the Hedgehog pathway (Robbins, two patents filed).