Christopher H. Lieu, MD is a clinician-scientist with strong training in translational colorectal cancer research with a strong commitment to developing new therapies for the treatment of metastatic colorectal cancer. Dr. Lieu is an Assistant Professor of Medicine in the Division of Medical Oncology at the University of Colorado Denver, where he serves as a bridge between the Gastrointestinal Medical Oncology and Developmental Therapeutics programs. His long-term career goal is to lead a multidisciplinary research team in translating preclinical biomarker discovery into more effective personalized medicine for patients with colorectal cancer. The candidate will develop expertise in translational clinical trial design and implementation, successful acquisition and interpretatio of correlative tissue studies, and advanced topics in bioinformatics through the K23 Mentored Patient-Oriented Career Development Award. The candidate's short-term career goal is to establish himself as an independent investigator in developmental therapeutics and gastrointestinal medical oncology with the preliminary data, research training, and publication record necessary to be competitive for NIH project grant funding. The K23 Mentored Patient-Oriented Research Career Development Award with help him to achieve these goals by: 1) granting him protected time to develop a clinical and translational research career under the guidance of a team of mentors dedicated to his success, 2) allowing him to receive specialized training in the design of biomarker-driven clinical trials, bioinformatics, and the responsible conduct of research through direct interaction with mentoring scientists and supplemental didactics, and 3) providing him the opportunity to gain recognition as a researcher in the field of drug development and colorectal oncology. His research plan aims to complete a phase I/IB study investigating a rationale combination of a MEK and Wnt inhibitor in patients with metastatic colorectal cancer. This study has been approved by the Cancer Therapy Evaluation Program (CTEP) and was the first trial opened under the new Experimental Therapeutics Clinical Trials Network (ET-CTN). A secondary aim of this study seeks to explore biomarkers of response in a concurrent preclinical study of these agents, as well as next-generation inhibitors, in patient- derived human tumor explants with a special interest in younger-onset colorectal cancer. Dr. Lieu has the full support of the University of Colorado Cancer Center who is funding the clinical trial (through the NCI UM1 grant) as well as the correlative and laboratory studies. Dr. Lieu has a mentorship team with expertise in colorectal cancer clinical trials, translational laboratory studies, drug development, preclinical biomarker development (Gail Eckhardt, MD, Wells Messersmith, MD), bioinformatics (Aik-Choon Tan, PhD), biostatistics (Patrick J. Blatchford, PhD, Edward Bedrick, PhD), and preclinical and scientific education (John Tentler, PhD). With his mentorship team, Dr. Lieu has developed a comprehensive career development plan to successfully transition from a mentored junior investigator to a fully-independent leader in the development of targeted therapies in patients with colorectal cancer.
Advances in chemotherapy, surgery, and radiotherapy have improved outcomes for patients with colorectal cancer. Unfortunately, mortality rates in the metastatic setting continue to be high, and new therapies are needed. The purpose of this study is to complete a clinical trial investigating the combination of selumetinib (AZD6244 hydrogen sulfate) in combination with cyclosporin A, with an expansion cohort of patients with refractory metastatic colorectal cancer. This proposal will also investigate biomarkers predictive of response in a preclinical trial in patient-derived human tumor explants utilizing the agents in the clinical trial as well as next generation targeted agents against the MAPK and Wnt pathways.
|Krishnamurthy, Anuradha; Dasari, Arvind; Noonan, Anne M et al. (2018) Phase Ib Results of the Rational Combination of Selumetinib and Cyclosporin A in Advanced Solid Tumors with an Expansion Cohort in Metastatic Colorectal Cancer. Cancer Res 78:5398-5407|