The AACR-KidneyCAN Kidney Cancer Innovation and Discovery Grant is a new grant mechanism that seeks to stimulate creative approaches to translate basic research into new treatment options for kidney cancer.

2025 Grantees

Scientific Statement of Research 

Most patients who die of kidney cancer do so due to metastatic disease. Dr. DeBerardinis and his team previously observed that metastases activate oxidative mitochondrial metabolism. In this project, he will evaluate the impact of a well-tolerated mitochondrial inhibitor, ONC201, on kidney cancer growth and metastasis in vivo. Additionally, he plans to use deuterium MRI,  a new non-invasive imaging tool, to monitor mitochondrial activity and assess the effects of ONC201 on these pathways.  This study may give rise to clinical trials in kidney cancer in the near term. 

Biography 

 Dr. DeBerardinis received his medical and doctoral degrees from the University of Pennsylvania and pursued clinical training at Children’s Hospital of Philadelphia in pediatrics and medical genetics. He is now professor and director of the Eugene McDermott Center for Human Growth and Development at UT Southwestern Medical Center. His lab studies altered metabolic pathways in cancer and inborn errors of metabolism. They use metabolomics and isotope tracing to characterize disease-associated metabolic states directly in patients, and mouse models to explore how metabolic perturbations contribute to tissue dysfunction. 

Acknowledgment of Support 

“I am grateful for this AACR KidneyCAN Innovation and Discovery Grant. It comes at a pivotal time in our efforts to understand kidney cancer progression and translate this knowledge into practice. We believe this grant project will provide foundational data for imaging and therapeutic clinical trials in kidney cancer.” 

Scientific Statement of Research

High-risk and relapsed Wilms tumors remain a major clinical challenge with poor outcomes. Dr. Petrosyan’s team has identified COL2A1, an extracellular matrix (ECM) protein absent in normal kidney but upregulated in aggressive tumors, as a potential driver of cancer stem cell (CSC) plasticity and chemoresistance. Their findings indicate that COL2A1 negatively regulates the tumor suppressor KLF4, facilitates epithelial-mesenchymal transition (EMT), and drives therapeutic resistance. Targeted inhibition of COL2A1 restores KLF4 expression, reverses EMT, and re-sensitizes CSCs to chemotherapy. Using CSC organoid cultures, patient-derived decellularized ECM scaffolds, and in vivo xenograft models, Dr. Petrosyan aims to elucidate the molecular mechanisms behind COL2A1-mediated KLF4 suppression and evaluate pharmacological KLF4 activation as a therapeutic approach in high-risk Wilms tumor.

Biography

Dr. Petrosyan earned her undergraduate degree from the University of California, Riverside, and her doctorate from the University of Southern California (USC). She completed her postdoctoral fellowship at Children’s Hospital Los Angeles (CHLA) and joined the faculty in 2022 as an assistant professor at USC/CHLA. Her research investigates extracellular matrix-driven mechanisms of cancer progression and chemoresistance, emphasizing the therapeutic targeting of cancer stem cells using advanced 3D in vitro models.

Acknowledgment of Support

“The ECM actively regulates tumor progression, therapy resistance, and cellular crosstalk within the tumor microenvironment. This AACR-KidneyCAN Innovation and Discovery Grant will support research into ECM-driven mechanisms in kidney cancer and foster interdisciplinary efforts to develop tumor microenvironment–targeted therapies with translational potential.”

Scientific Statement of Research

Translocation renal cell carcinoma (tRCC) is an aggressive kidney cancer that affects both adults and children and is driven by gene fusions of the TFE3 transcription factor. While TFE3 fusions create critical oncogenic dependencies in tRCC, direct targeting of TFE3 is challenging because it is a transcription factor with many disordered regions. Dr. Viswanathan and his team developed a phenotypic screening strategy to identify small molecules that disrupt TFE3-chromatin interactions essential for oncogenesis. Screening 25,000 compounds identified 62 hits, with compounds acting via two complementary mechanisms: retention/trapping of TFE3 on chromatin or displacement of TFE3 from chromatin. Dr. Viswanthan will focus on further functional validation of these hits and mechanistic characterization via a suite of cell-based and biochemical deconvolution assays. This effort aims to establish a robust pipeline for screening for TFE3 inhibitors, paving the way for future large-scale screens with the development of a first-in-class targeted therapy for tRCC.

Biography

Dr. Viswanathan is an MD/PhD graduate of Harvard Medical School. He completed his residency in internal medicine at the Massachusetts General Hospital and his fellowship in hematology/oncology at Dana-Farber/Harvard Cancer Center. He is a genitourinary medical oncologist at Dana-Farber Cancer Institute and an associate professor of Medicine at Harvard Medical School. His laboratory uses genomic and functional genetic technologies to discover the molecular underpinnings and vulnerabilities of cancer, with focus on cancers of the kidney and prostate, and a special emphasis on rare kidney cancer subtypes including translocation renal cell carcinoma.

Acknowledgment of Support

“This award will help establish foundational data to support efforts in discovering inhibitors of TFE3 fusions for translocation renal cell carcinoma, a kidney cancer of great unmet need that currently lacks specifically approved therapies.”

2024 Grantees

Research

Human endogenous retroviral (HERV) antigens are considered leading candidates to account for a higher immune checkpoint inhibitor response rate for clear cell renal cell carcinoma (ccRCC) than predicted by its low mutation and neoantigen density. Four candidate hERV-encoded HLA-A2 epitopes recognized by spontaneously arising CD8+ T cells have been identified in breast cancer patients. T-cell responses arising in ccRCC patients targeting these broadly shared HLA-A2-associated hERV antigens have not been investigated and would be of great interest. Dr. Warren and his team plan to identify and quantify T-cell reactivity for hERV-encoded, HLA-A2 associated T-cell epitopes spontaneously arising in HLA-A2+ RCC patients and assess the anti-tumor potency of these T cells. Validation of spontaneous T-cell immunity targeting hERV can be translatable to future vaccine or engineered T cell-based therapies.

Biography

Dr. Warren received his bachelor’s, medical, and doctoral degrees from Harvard University. He is now an oncologist and cancer immunologist with a focus on cellular and molecular dissection of antitumor immune responses and also the program head for Global Oncology at the Fred Hutchinson Cancer Center. His lab has long been interested in harnessing the exquisite specificity and potency of T cells to recognize and eliminate cancer. Another major focus of his lab’s effort has been on the immunobiology of kidney cancer and the development of T-cell therapy for advanced kidney cancer.

Acknowledgment of Support

“Kidney cancer is known for its sensitivity to immune therapy and developing antigen-specific therapy for kidney cancer is a major focus of our laboratory. The AACR-KidneyCAN Kidney Cancer Innovation and Discovery Grant will support the development of immune therapy for kidney cancer that targets the protein products of human endogenous retroviruses.”

Research

Most clear cell renal carcinoma (ccRCC) cases are associated with the inactivation of VHL protein, which leads to the stabilization and accumulation of HIF-2α protein. The HIF-2α inhibitor belzultifan was recently developed and approved by the FDA to treat advanced RCC patients. However, both intrinsic and adaptive resistance to this drug were reported in preclinical studies using kidney cancer cell lines or xenograft models. By generating a HIF-2α inhibitor adaptive resistant ccRCC cell line model, Dr. Zhang plans to identify potential targetable pathways that may contribute to HIF-2α inhibitor resistance. Through further mechanistic studies, he aims to identify potential therapeutic options that can reverse drug resistance to HIF-2α inhibitor in ccRCC.

Biography

Dr. Zhang obtained his undergraduate degree from Wuhan University in China, and his doctoral degree from University of Pittsburgh School of Medicine. He worked as a postdoctoral fellow and an instructor at the Dana Farber Cancer Institute. He became an assistant professor at UNC Chapel Hill in 2013 and was promoted to associate professor in 2019. He is an associate professor with tenure in the Department of Pathology at UT Southwestern Medical Center.  

Acknowledgment of Support

“Belzultifan, a HIF-2a inhibitor was approved by the FDA to treat advanced RCC. However, both intrinsic and adaptive resistance was reported, posing critical clinical challenges. This award will help generate vital preliminary data, uncovering the mechanisms underlying drug resistance and developing alternative treatments for HIF-2a inhibitor-resistant patients in kidney cancer.”