Hepatocellular carcinoma, the most frequent type of liver cancer, is a major health problem and represents the second leading cause of cancer-related death in the United States. Although the treatment of hepatocellular carcinoma has greatly improved over the last decades, most patients diagnosed at advanced stages are ineligible for curative therapies such as surgical removal of the tumor or liver transplantation. For those patients, the sole therapeutic option is a drug called sorafenib, which only improves survival from 8 to 11 months, emphasizing the urgent need for novel therapeutic strategies. Cancer therapy is often hampered by reduced drug efficacy or the rapid emergence of drug resistance, and as a consequence, treatment with single drugs is condemned to failure. It is therefore clear that we must identify new drug combinations to improve the clinical management of this deadly disease. Here, our objective is to identify and test effective combination therapies with palbociclib, a powerful drug that stops the growth of cancer cells, for liver cancer treatment. This drug has shown outstanding effects in breast cancer patients and is currently in clinical trials for advanced hepatocellular carcinoma patients. Moreover, palbociclib presents reduced toxicity and is therefore a good candidate for combination therapies. The rationale for the proposed research is that, by identifying drugs that enhance the efficacy of palbociclib and/or overcome resistance to palbociclib, we will improve the treatment options of liver cancer patients and our understanding of liver cancer biology.
The overarching goal of my research program is to discover and validate new combination therapies with increased efficacy for hepatocellular carcinoma. This Career Development Award will provide me with support to address important biologically and clinically relevant questions in the field of liver cancer during the first years of my tenure-track appointment. To achieve my goals, I will work closely with my mentor, Dr. Friedman, the Dean for Therapeutic Discovery and Chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai. We have designed a career development plan that will help me develop the proper skills to launch a successful career in liver cancer research and reach the proposed goals. By discovering novel combination therapies for hepatocellular carcinoma, we will improve the therapeutic options of advanced liver cancer patients, which currently present reduced survival. I predict that it will take 3 years to complete our proposed project and to be translated into a clinical trial. The successful completion of these studies will particularly benefit the US Military and Veterans community. Most of the main risk factors for hepatocellular carcinoma, such as alcohol consumption, hepatitis B and C infection, obesity, and male gender, are over-represented within the US Military and US Veterans community. I anticipate that our project will uncover novel pharmacological combination therapies for hepatocellular carcinoma and produce a blueprint that can be applied to other drugs and other tumor types.
|Effective start/end date||1/01/15 → …|
- Congressionally Directed Medical Research Programs: $610,200.00