Leight awarded Pelotonia funded grant for cancer research
The vast majority of druggable targets identified by in vitro screening using traditional cell culture methods on plastic plates do not translate to clinical success. To overcome this obstacle, numerous studies have demonstrated that three dimensional (3D) cell culture, which more closely mimics the in vivo microenvironment, better predicts drug efficacy as compared to traditional two dimensional (2D) culture. However, these in vitro methods use immortalized homogeneous cell lines, which lack the heterogeneity and variability in treatment responsiveness observed in vivo, both patient to patient and variability in cells of the same tumor. Therefore, new technologies are needed that enable in vitro experimentation of more relevant tumor models. To address this need, we are developing the core capabilities for a 3D cell culture platform in which one can culture microexplants of human tumor tissue while simultaneously measuring cell viability and matrix metalloproteinase (MMP) activity. Here, we will conduct a pilot drug screen to assess the effects of current treatments on MMP activity of human breast cancer microexplants cultured in an in vitro hydrogel system. We will leverage the strength of our interdisciplinary team with expertise in biomaterials assay development, cancer cell pathology, and oncology to develop these cutting edge 3D hydrogel culture systems. Achieving the objectives outlined here will address significant barriers in the field, and future applications are far reaching, not only for screening cancer therapeutics, but also in other contexts in which MMP activity plays an important role, such as heart disease, arthritis, and tissue regeneration.
This project is the work of a highly interdisciplinary collaboration with co-PIs Dr. Clara Lee - Department of Plastic Surgery, Dr. Daniel Stover - Department of Internal Medicine, and Dr. Rulong Shen - Department of Pathology of the OSU College of Medicine.