Medical Oncologist, Federation University, Australia
Title: Epithelial-to-Mesenchymal Transition (EMT) as a Robust Biomarker and a Novel Strategy to enhance response to Immune Checkpoint Blockade and Targeted therapy in patients with Metastatic Renal-Cell Carcinoma (mRCC)
After earning his medical degree, Prashanth pursued Medical Oncology training at Calvary Mater Newcastle Hospital, he furthered his education and completed training with a Fellowship in Medical Oncology at The Austin Hospital in Melbourne. Prashanth has extensive research experience and his other qualifications apart from FRACP & PhD (University of Melbourne) include Masters of Science (Biotechnology) from University of Western Sydney and Master of Public Health (Epidemiology and Statistics) from the University of Newcastle. Prashanth has presented at major national and international meetings, and authored publications in prominent cancer related peer reviewed journals. He has a special interest in transitional research and immunotherapy, and is a lead investigator in a number of clinical trials, and also is involved in development and conduct of clinical trials. His research goals are to develop innovative models to establish EMT mechanism as an important biomarker for cancer progression, resistance to therapy and as a biomarker of responsiveness to immune therapy, with the aim of developing/designing EMT-based therapies in cancer.
Epithelial-to-Mesenchymal Transition (EMT) is a dynamic and reversible process hypothesized to occur in carcinoma during invasion and metastasis. EMT transformed carcinomas carry poor prognosis and are hypothesized to resist therapy. It is becoming increasingly evident that the immune system plays a critical role in cancer progression, resistance to therapy and relapse. The recent discovery of immune checkpoints and the regulatory approval of immune checkpoints inhibitors (ICI) have revolutionized the treatment of patients with metastatic renal cell carcinoma (mRCC). Several recent clinical trials have shown that ICI can induce durable long-term response and prolong overall survival. However, significant number of patients can develop severe dose limiting immune related adverse effects and a large subgroup of patients do not respond to ICI therapy. We hypothesize that EMT is a contributing factor to resistance to ICI, including VEGF inhibitors and mTOR inhibitors, which currently remains standard of care in treatment of patients with mRCC. We propose that EMT plays a role in intrinsic and/or acquired resistance to ICI by modulating sensitivity to immune modulation, as tumors de-differentiate to a mesenchymal phenotype, contributing to development of therapy resistance and early recurrence of tumours. The potential impact of EMT is of limiting Progression Free Survival and Overall Survival in patients with mRCC. Results will be presented to confirm EMT mechanism as an important biomarker for renal cancer progression, and responsiveness to therapy, including immune check point inhibitors and VEGF inhibitors. Our current study also involves determining development of EMT signature in circulating tumour cells of mRCC patients; an approach which would aid in determining development of resistance to therapy prior to clinical progression in patients with mRCC. Also, results of a comprehensive analysis of immune check points, and the predictive power of these new immune modulators compared to the ones currently used in clinical trials will be presented. In addition to predicting worse outcomes, the signature has a potential to act as a biomarker to stratify patient population who will benefit the most with checkpoint inhibition, thus opening new avenues to design clinical trials with aim of individualising treatment for patients with mRCC. The novel strategy of targeting EMT in mRCC has a potential to reinstate host immune response, resulting in enhanced sensitivity to immune modulation and targeted therapy, and EMT, as a mechanism of intrinsic or acquired resistance, has the potential to be a robust predictive and prognostic marker in patients with mRCC