Dr. Naga Vara Kishore Pillarsetty, Memorial Sloan Kettering Cancer Center, USA

Improving Diagnosis and Treatment of Metastatic Castration Resistant Prostate Cancer

The seminar will focus on how our lab is developing simple radiochemistry and chemistry based solutions for improving disease classification using non-invasive imaging and develop appropriate treatments for disease using prostate cancer as a case study. Primary prostate cancer begins as androgen receptor (AR) driven disease that can be effectively controlled by androgen deprivation therapy (surgery and/or castration) followed by androgen receptor signaling inhibition. Resistance is inevitable and a subset of these patients will progress to metastatic castration resistant prostate cancer (mCRPC) stage that is incurable. mCRPC represents a collection of heterogenous tumors that have very different phenotype, can display androgen independence and therefore completely resistant to treatment. We are developing antibody (mAb) based PET (Positron Emission Tomography) imaging and radiotherapeutic agents to aid identification, classification, and treatment of these disease subtypes. The antibodies target unique cell surface antigens that are selectively expressed on the tumors and carry either a diagnostic or therapeutic radioisotope. In addition, we are developing methods to reduce severe side effects (salivary gland toxicity) caused by prostate specific membrane antigen (PSMA) targeting radiotherapeutic agents [177Lu]-Lu-PSMA-617 (Pluvicto® - recently approved in US) and highly efficacious agent [225Ac]-Ac-PSMA-617 that is undergoing clinical trials. On the optical imaging front, we are developing nerve imaging agent that is based on a tarantula spider venom derived peptide Tsp1a. In prostate cancer front, it can assist in identifying nerves that can aid in better resections of prostate that will aid in minimizing incontinence and impotence that are associated with prostatectomies. The talk will highlight some of the progress we made on these fronts in animal models and human studies that we believe will ultimately improve survival and quality of life for the patients.