The Kidney Cancer Association has announced the recipients of the Advanced Discovery Awards (ADAs) and Young Investigator Awards (YIAs). In April, the Kidney Cancer Association approved $1.3 million in new grant funding to advance early detection and new treatments of kidney cancer.

Established this year, the purpose of the ADA is to promote collaboration between a clinician and a PhD to propose new research that will make an immediate impact in the field of kidney cancer. The YIA seeks to encourage promising researchers in urology and clinical oncology who are planning to pursue an investigative career in kidney cancer. ADAs are for established investigators, and, this year, two grants of $500,000 were awarded. In addition to these new grants, the Kidney Cancer Association increased the number and value of the YIAs from two grants worth $50,000 to four grants worth $75,000.

All grant proposals were initially evaluated through a letter of intent. Top-ranking letters of intent were invited to submit a full proposal. An independent panel of reviewers conducted a scored review of all applications received.

The first installment of awards will be distributed in October 2019. A select number of recipients will present their projects to physicians, researchers, and medical staff from leading centers across the globe at the 19th International Kidney Cancer Symposium in November 2020.

ADA Recipients

Kathleen M. Mahoney, MD, PhD, of Dana-Farber Cancer Institute, Beth Israel–Deaconess Medical Center; Gordon J. Freeman, PhD, of Dana-Farber Cancer Institute; and Rupal S. Bhatt, MD, PhD, of Beth Israel–Deaconess Medical Center received the first ADA for their project titled, “HHLA2/KIR3DL3 as a Novel Therapeutic Immune Checkpoint Pathway in Renal Cancer.”

This research team will explore a novel immune checkpoint pathway that is similar to, but nonoverlapping with, the PD-1/PD-L1 (programmed cell death protein 1/programmed cell death ligand 1) pathway, which has been the key driver of advances in immunotherapy. A better understanding of how this HHLA2/KIR3DL3 pathway works and determining whether disrupting it allows immune cells to target and destroy cancer cells could be particularly important for patients with metastatic renal cell carcinoma who might not benefit from existing immunotherapies.

Eric Jonasch, MD, and Guang Peng, PhD, both of The University of Texas MD Anderson Cancer Center, Houston, were awarded the second ADA for their project, “S-Phase DNA Damage Response Links Genomic Instability Mechanisms to Antitumor Immunity in Renal Cell Carcinoma.”

This research team will investigate how the novel tumor-suppressor gene NPRL2 functions. The team will study how NPRL2 triggers an innate immune response in renal cell carcinoma through impairing S-phase DNA damage response. NPRL2 is frequently deleted from chromosomes in clear cell renal cell carcinoma, and the research team will also explore treatment strategies exploiting this deficiency.

YIA Recipients

The first YIA recipient is Scott M. Haake, MD, who was mentored by W. Kimryn Rathmell, MD, PhD, both of Vanderbilt University Medical Center, for work titled, “Endogenous Retrovirus Expression Drives Immunogenicity of Papillary Renal Cell Carcinoma.”

In prior published work, Dr. Haake and colleagues established that endogenous retroviruses are a biomarker for immune response in patients with clear cell renal cell carcinoma and a potential therapeutic target. This research project will shift focus to investigate expression of endogenous retroviruses in papillary renal cell carcinoma (both types 1 and 2) to and how endogenous retroviruses impact antitumor immune response in this understudied subtype of renal cell carcinoma.

The second YIA recipient, Akash Kumar Kaushik, PhD, was mentored by Ralph J. DeBerardinis, MD, PhD, both of The University of Texas Southwestern Medical Center. Dr. Kaushik’s project is titled, “In Vivo Glutamine Metabolism in VHL- and FH-Mutant Renal Cell Carcinoma.”

Dr. Kaushik’s research project will take a closer look at the amino acid glutamine and its role in cellular activity. In particular, he will investigate the efficacy of a glutaminase inhibitor in patient-derived mouse models with mutated versions of the VHL and FH tumor-suppressor genes. Dr. Kaushik will also examine how effective specific inhibitors of a key energy-generating cellular process are in VHL- and FH-mutant tumors.

The third YIA was awarded to Ed Reznik, PhD, who was mentored by A. Ari Hakimi, MD, both of Memorial Sloan Kettering Cancer Center. Dr. Reznik’s work is called, “Metabolic Determinants of the Tumor Microenvironment and Sensitivity to Immunotherapy in Clear Cell Renal Cell Carcinoma.”

The tumor microenvironment plays an important part in in the effectiveness of immunotherapy. Dr. Reznik will closely examine tumor metabolism as it relates to the tumor microenvironment of clear cell renal cell carcinoma. A better understanding of the tumor microenvironment and its varied components might help indicate which therapies are more likely to be effective for patients with clear cell renal cell carcinoma, thereby avoiding potentially unnecessary treatment. The findings also have the potential to identify new therapeutic targets.

Tian Zhang, MD, MHS, mentored by Daniel J. George, MD, both of Duke Cancer Institute, received the fourth YIA for the project, “Immune Correlates of Immunotherapy Responses in Renal Cell Carcinoma.”

Patients with metastatic clear cell renal cell carcinoma have several options when it comes to first-line immunotherapy, including combination treatment with vascular endothelial growth factor inhibitors. Choosing between options is still a challenge. Dr. Zhang will analyze how the tumor microenvironment responds to immunotherapy. In addition, Dr. Zhang will investigate a panel of five genes and their association with resistance to ipilimumab/nivolumab combination therapy. ■