Dr. South is a molecular biologist studying squamous cell carcinoma, particularly those arising in individuals with genetic predisposition to progressive disease. His experimental approach centers on the use of human primary cells and derived early passage cell lines to understand mechanisms driving tumor initiation and progression.
Tissue Damage-Driven Squamous Cell Carcinoma
This project focuses on understanding how mechanisms associated with chronic tissue damage influence the development and progression of squamous cell carcinoma (SCC). Our proposal builds on our previous findings that similarities exist between a rare genetic SCC disease model, recessive dystrophic epidermolysis bullosa (RDEB) and metastatic subtypes of sporadic head and neck SCC. Our goal is to identify and characterize the molecular events contributing to tumor initiation and progression in the context of tissue damage, with the over- arching aim of uncovering potential new avenues for the effective prevention and treatment of SCC. Funding: National Cancer Institute Project No. 5R01CA244522-03.
Rigosertib for recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma
Squamous cell carcinoma (SCC) of the skin is the biggest cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies which target RDEB SCC are urgently required. We previously identified a lead compound, ON-01910 (rigosertib) that exhibited significant specificity for RDEB cancer: rigosertib induced apoptosis in 10/10 RDEB SCC keratinocyte populations without affecting normal RDEB skin cells in culture. Based on this data we initiated a "first in EB" clinical trial of rigosertib to assess tolerability and tumor targeting in patients with late stage, metastatic and/ or unresectable SCC. The first patient to be treated with rigosertib in Europe has shown a complete response with all three target lesions being eliminated after six months. This application is to fund treatment of three patients in the US with intravenous rigosertib. Funding: EB Research Partnership
Targeting fibrosis for Recessive Dystrophic Epidermolysis Bullosa Therapy
This project screens FDA approved compounds for efficacy in reducing pro-tumorigenic fibrosis using in vitro tissue engineering models of RDEB extracellular matrix and the RDEB hypomorphic mice. Funding: EB Research Partnership and EB Medical Research Foundation.