Collaborative efforts between the highly ranked School of Pharmacy at the University of Kansas and several regional partners, including the Stowers Institute of Medical Research, provide the strength for innovative discoveries in oncology treatment. KU has strong capabilities in high throughput screening, combinatorial chemistry, bioinformatics, structural biology, imaging, analytical and process chemistry in large part due to three NIH funded grants. Committed to gaining knowledge in the lab and translating discoveries to the clinic allows Kansans access to emerging therapies through the clinical trials program.
Improving access to these clinical trials is the key driver in the University's plan for delivering comprehensive cancer care and achieving NCI designation. In order to improve this access, infrastructural developments committed to the management and development of clinical trials are a significant part of the KU Cancer Center. The Cancer Center manages seven shared core facilities that support the research programs and member investigators. These resources include: Biospecimen, Biostatistics, Biotechnology Innovation and Optimization, Clinical Trials Office, Drug Discovery and Development Project Management, Flow Cytometry, and High Throughput Screening.
The Department of Otolaryngology at the University of Kansas is committed to offering its patients the most advanced therapies available in all of the Otolaryngology sub-specialties. The Director of Clinical Research serves as the key facilitator for the development of new investigator initiated trials and participation in multi-center trials. Assistance is available for all aspects of clinical trials including: protocol development, statistical analysis, clinical research coordination, regulatory document management, Institutional Review Board compliance management, and poster/manuscript preparation.
Over the last several years the department has participated in numerous clinical trials and continues to provide opportunities for patients to enroll in prospective trials for various diagnoses. Specifically for our Head and Neck patients these trials have included innovative therapeutics, quality-of-life assessment, and supportive care interventions.
We are excited to establish a new program in H&N Basic Science Research. Dr. Sufi Thomas from the University of Pittsburgh joined us in July 2013 to lead the program.
Overview of the Translational Research Work in the Laboratory of Dr. Sufi Thomas
Despite improvements in conventional therapies, head and neck cancer continues to be a major challenge with poor 5-year survival rates. Dr Thomas' main focus has been to understand the biological mechanisms involved in head and neck squamous cell carcinoma (HNSCC) progression and to develop effective therapeutic interventions. In order to better understand HNSCC biology, it is important to examine the supportive environment that the tumor cell exist in. Several non-tumorigenic cells constitute the cellular stromal environment surrounding the tumor including fibroblasts, immune cells, cells that form blood vessels (endothelial cells and pericytes) and neuronal cells. Fibroblasts are the most abundant stromal type in HNSCC. Emerging evidence demonstrates molecular cross talk between HNSCC and fibroblasts that increase tumor growth, invasion into surrounding tissue and metastasis. Dr. Thomas is in the process of identifying signaling molecules involved in the cross-talk between HNSCC and fibroblasts in order to block tumor growth and metastasis. The finding from these studies has tremendous potential in target identification and therapeutic development. One of the impediments to cancer therapy is the lack of inhibitors specific to emerging molecular targets.
Gene therapy with antisense oligonucleotides can be used to specifically target molecules that are important for tumor growth. Dysregulation of growth factor receptors including the epidermal growth factor receptor (EGFR) in HNSCC results in a promotion of growth. Several EGFR inhibitors currently in clinical trials that inhibit receptor activation and function have demonstrated limited antitumor efficacy. An alternate approach is to reduce the levels of the EGFR protein using antisense gene therapy. Although intra-tumoral administration of EGFR antisense gene therapy has been demonstrated to have antitumor efficacy in a phase 1 clinical trial, intratumoral injections are not a viable route of administration for tumors that are metastatic or difficult to access. Traditional antisense DNA or RNA based molecules cannot be administered systemically due to rapid degradation by serum enzymes. To circumvent this problem, we have developed antisense agents with a pseudo-peptide backbone called guanidinium-peptide nucleic acid (GPNA). This novel class of molecules is resistant to enzymes in serum and has a strong affinity for complementary DNA and RNA sequences. We have designed a GPNA antisense oligomer complementary to EGFR mRNA (EGFRAS GPNA). EGFRAS GPNA treatment results in tumor growth inhibition on systemic delivery in animal models. Identification of other targets with therapeutic potential that lack specific inhibitors is currently underway. This method of systemically delivered antisense oligonucleotides holds immense potential for personalized cancer therapy.
Potential Opportunities for Laboratory Research: Residents and Fellows are encouraged to participate in basic science or translational research pertaining to the main focus areas of the laboratory.