DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Systemic Characterization of Kidney Cancer Tumor Suppressors in Modulating Metastasis and Response to Immunotherapy

Principal Investigator: MANGALVEDHEKAR, AMRITA
Institution Receiving Award: SLOAN KETTERING INSTITUTE FOR CANCER RESEARCH
Program: KCRP
Proposal Number: KC200185
Award Number: W81XWH-21-1-0778
Funding Mechanism: Academy of Kidney Cancer Investigators - Early Career Scholar Award
Partnering Awards:
Award Amount: $1,283,229.00
Period of Performance: 9/30/2021 - 9/29/2025


PUBLIC ABSTRACT

Kidney cancer is the 8th most common cancer in the world, with ~400,000 new cases diagnosed every year, and 6th most common cancer in the U.S., with ~60,000 cases annually. There are ten distinct types of kidney cancer. The most lethal form of kidney cancer, clear cell renal cell carcinoma (ccRCC), is aggressive because it can spread to distant sites (metastasis). Genetic alterations such as mutations are known to drive tumorigenesis as well as response to ongoing therapy. Although genetic alterations occurring in primary kidney cancer have been studied, mutations at the distant metastatic site are unknown. We propose that genetic alterations occurring at distant lesions likely aid in acquiring the ability to become metastatic. In this project, we will find the effect of mutations-driven gene deficiency on its ability to cause metastasis or response to immunotherapy. We will also evaluate the mechanism due to which these genetic alterations can cause disease progression and therapy resistance. Our study will advance kidney cancer research tremendously by finding a genetic alteration-driven spread of primary kidney cancer to distant sites, cause of resistance to current treatments, and predictive biomarker to determine the efficacy of treatment.

The investigator's central theme is to find why some kidney cancers patients develop metastasis and succumb to disease as well as understand the reason why some patients become refractory to treatment. Answers to these two questions will aid in the development of new therapeutics enabling long-term response and better management of disease, a step closer to the final goal of finding a cure for kidney cancer. Funding obtained from the DOD Kidney Cancer Research Program Academy of Kidney Cancer Investigators (AKCI) Early-Career Investigator Award, advice from a designated mentor, and a strategic plan will lead to the successful execution of the proposed research. The investigator will participate in the AKCI virtual career development program to conceive new ideas, learn and share new techniques, and find collaborations to work towards the common goal of finding a permanent cure for kidney cancer. Ultimately, with this collective initiative, we will identify novel drug targets that cause distant metastasis or resistance to treatment. The proposed research will enable us to translate our therapeutic idea from lab bench to bedside within a short span.