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.”