Otolaryngology and Cancer Biology
Bachelors: Bombay University, India
Masters: Mumbai University, India
PhD: Mumbai University, India
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Office Line (913) 588-6664
Lab Phone (913) 945-6579
Understanding 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.
Shary Shelton, PhD
Vikalp Vishwakarma, PhD
Sufi Thomas, Ph.D.
3020A Wahl Hall East, Mail Stop 3010
3901 Rainbow Boulevard
Kansas City, KS 66160
(913) 588-6664 Lab Phone (913) 945-6579