Supporting the Future of Kidney Cancer Research

Challenge

Clear cell RCC may exploit an alternative energy pathway to survive in low-oxygen environments.

Funded Approach

Use patient samples, metabolomics, and mouse models to determine how tumors produce and use rhodoquinone—and whether blocking the pathway slows growth.

Potential Impact

Reveal a previously unrecognized metabolic vulnerability and open new paths for diagnosis and treatment.

Researcher Perspective

“This grant provides critical support to pursue high-risk, high-impact research in kidney cancer metabolism.”

Challenge

Translocation RCC is a rare, aggressive cancer with poor responses to standard therapies and no validated surface target for radioligand theranostics.

Funded Approach

Quantify CDH17 expression, validate CDH17-immunoPET as a biomarker, and test CDH17-directed radioligand therapy in patient-derived models.

Potential Impact

Generate the evidence needed to advance a targeted imaging-and-treatment strategy toward clinical translation.

Challenge

HLRCC is a rare, aggressive kidney cancer driven by FH loss. Its tumors show elevated ribosome biogenesis, but this process has historically been difficult to target safely.

Funded Approach

Develop small-molecule inhibitors against a newly identified nucleolar complex that is highly upregulated in FH-mutant tumors.

Potential Impact

Establish a tractable, cancer-specific therapeutic strategy for HLRCC.

Research Summary

The Incidence of renal cell carcinoma (RCC) continues to increase in the United States, ranking among the ten most frequently diagnosed cancers in men and women. Unfortunately, resistance to existing treatments remain a major obstacle, driving the need for identification of clinically relevant biomarkers and therapeutic targets. TNF-related apoptosis inducing ligand (TRAIL) is a promising cancer therapy that selectively induces apoptosis in malignant cells while sparing normal cells. TRAIL exerts its cytotoxic effects through binding death receptors DR4 and DR5, initiating caspase dependent programmed cell death. However, intrinsic and acquired resistance mechanisms have limited TRAIL’s efficacy as anti-cancer strategy. We have identified a link between the overexpression of oncogenic PIM kinases and regulation of DR5 expression and sensitivity to TRAIL apoptosis in RCC. PIM1 is emerging as a clinically relevant biomarker and therapeutic target in RCC. Nuvisertib (TP-3654) is a selective PIM1 kinase inhibitor currently being evaluated in Phase 1/2 clinical trials for patients with myelofibrosis and has received FDA fast track designation. We find that treatment of RCC cells with low dose (2.5 µM) of Nuvisertinib over 24 hours induces a 5.75-fold (p<0.01) increased mean membrane expression of DR5 compared to vehicle control assessed by flow cytometry. We also investigated synergism between Nuvisertib and Dordaviprone, a newly FDA approved imipridone and TRAIL inducer. We evaluated combinations of Nuvisertib and Dordaviprone via Cell Titer Glo in RCC cells and find that combination indices indicate synergism which significantly reduce RCC cell viability more potently than either agent alone. Our findings highlight actionable novel candidate targets and strategies for therapeutic intervention in RCC. Ongoing studies are aimed to uncover mechanistic insights of these treatments in RCC and guide the development of optimal treatment strategies.

Personal Statement

My long-term goal is to become an independent cancer biology research investigator. I am currently a 6th-year PhD student at Brown University mentored by Dr. Wafik El-Deiry, director of the Legorreta Cancer Center. My thesis focuses on identifying dysregulated signaling pathways in renal cell carcinoma (RCC) to validate novel biomarkers and develop more efficient anti-cancer strategies. My research has found that the emerging biomarker oncogenic PIM-1 kinase is regulated via an actionable IL-6/JAK/STAT3 axis in ccRCC. Presented at a previous AACR meeting, this work is now in revision for publication. I am now evaluating the inhibition of PIM kinases to re-sensitize RCC cells to TRAIL apoptosis. I have identified and submitted an abstract describing a potent synergism between TP-3654, an FDA fast-tracked PIM1 inhibitor, and ONC201, a newly FDA-approved imipridone TRAIL inducer discovered by Dr. El-Deiry. The targeting of PIM1 and reactivation of TRAIL apoptosis in RCC is a novel combination strategy that could address therapy resistance in RCC and be developed as a more accessible treatment with FDA designations. The AACR-Kidney Cancer Collaborative Scholar-In-Training award is clearly aligned with my goals and would allow me to i) disseminate my doctoral research, ii) expose me to novel research, and iii) empower me to network with peer and senior leaders at AACR. It would be my honor and privilege to be selected for this award and gain access to a distinguished network.

Research Summary

The presence of sarcomatoid (Sarc) and rhabdoid (Rhab) dedifferentiation in renal cell carcinoma (RCC) is linked to poor clinical outcomes and higher risk of metastatic disease. Previous molecular studies on renal tumors with these dedifferentiated features lacked spatial resolution to distinguish these aggressive regions from classical RCC histology, leaving the biology underlying these aggressive phenotypes poorly understood. We applied spatial whole transcriptome profiling (GeoMx DSP) to 370 regions exhibiting Sarc, Rhab, clear cell, papillary, or benign kidney from 54 RCC tumors. We combined these spatial transcriptome profiles with our single-cell RNA-sequencing atlas consisting of different RCC subtypes to investigate Sarc/Rhab biology and verified clinical significance of our findings using public databases such as The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Deconvolution of the spatially resolved transcriptome data revealed substantial gene expression reprogramming in Sarc/Rhab regions. Notably, Sarc/Rhab areas featured a high fibroblast-like gene expression pattern and a loss of cytokeratin expression as a defining hallmark of Sarc and Rhab dedifferentiation, reflecting their histological nature. We established cancer cell-intrinsic gene expression signatures of Sarc and Rhab tumors and found they are highly correlated with higher tumor grade in the ccRCC cohorts from both TCGA (n=485) and CPTAC (n=103). Importantly, these signatures significantly predicted poor disease-free survival in clinically low-risk (Stage 1-2) ccRCC patients. In the ccRCC cohort of TCGA, tumors with high Sarc gene signature levels were enriched for mutations in SETD2, PTEN, MTOR, and KDM5C, as well as specific copy-number variations, notably loss of 14q, 9, 18, and 6p and gain of 20, 12, and 8q, compared to other tumors. Pathway enrichment analyses suggested that genes related to extracellular matrix organization, coagulation, and epithelial-mesenchymal transition were highly enriched in Sarc/Rhab regions compared to classical ccRCC regions, while pathways for oxidative phosphorylation, adipogenesis, and amino acid metabolism were decreased.These findings provide novel insights into the biology of Sarc/Rhab dedifferentiation in RCC, paving the way for the development of improved prognostic markers and targeted therapeutic strategies.

Personal Statement

My thesis leverages single-cell and spatial transcriptomics to dissect the biology of aggressive renal cell carcinoma (RCC) subtypes, specifically sarcomatoid (Sarc) and rhabdoid (Rhab) dedifferentiation. My research addresses a critical gap: translating specific histopathological changes into molecular profiles. The submitted research is highly relevant to scientific and clinical advances in these aggressive phenotypes. By presenting novel findings such as the fibroblast-like genetic shift and a gene signature predictive of progression in early-stage RCC cases, I provide crucial insights for developing quantitative, unbiased diagnosis and identifying potential therapeutic targets co-targeting the tumor and its microenvironment. Presenting at the AACR is vital for knowledge mobilization. I aim to share progress on this clinically unmet need with leading colleagues and pharmaceutical companies interested in novel targets for aggressive RCC. I also expect to meet potential collaborators in AI-based digital pathology to develop spatial transcriptomics-guided AI models capable of detecting subtle micro-dedifferentiations in minimally invasive biopsy samples. My long-term career goal is to become an independent Investigator dedicated to translational genomics in oncology. Drawing on my biotech co-founder experience and academic research, I aim to bridge advanced computational data (like spatial multi-omics) with clinical pathology to develop next-generation precision medicine.

Research Summary

SMARCB1-deficient renal medullary carcinoma (RMC) is a highly aggressive kidney cancer characterized by replication stress and proteotoxic vulnerabilities, yet the molecular determinants of therapy response remain poorly understood. To delineate the mechanisms of response and resistance, we performed integrative single-cell and bulk multi-omic profiling of tumor samples from patients with RMC treated with a combination of the proteasome inhibitor ixazomib, gemcitabine, and doxorubicin. Analysis of 33,410 single cells from 11 patients revealed pronounced intratumoral and microenvironmental heterogeneity. Responding tumors displayed immune-inflamed microenvironments enriched for CD8⁺ cytotoxic T cells, effector-like and Tfh CD4⁺ T cells, NK cells, plasmacytoid (pDC) and conventional dendritic cells (cDC1/cDC2), and S100A8⁺ monocytes, consistent with enhanced antigen presentation and effector activation. In contrast, non-responders exhibited abundant macrophages, regulatory T cells, plasma cells, and inflammatory and myofibroblastic cancer-associated fibroblasts (iCAFs/mCAFs), forming immunosuppressive stromal-myeloid circuits that impeded cytotoxic infiltration and response. Malignant cells segregated into six transcriptional states, including proliferative, hypoxia-responsive, epithelial-mesenchymal, and neuroendocrine-squamous hybrid lineages. A proliferative state marked by replication stress, unfolded-protein-response activation, and proteasome component upregulation was enriched in non-responders and persisted at progression, suggesting adaptive proteostasis-driven resistance. Copy-number analyses identified focal gains in BAG4, UBE4B, and UBE2W that may enhance apoptosis evasion and p53 degradation, reinforcing proteotoxic resilience. In contrast, well-differentiated and immune-mimicry tumor states correlated with improved survival. Integrative cell-cell communication analysis highlighted stromal-immune signaling through BMP4/5 and WNT4/6 as a hallmark of resistant tumors, whereas BMP6 expression associated with dendritic-cell activation and favorable immune remodeling. Together, these findings define molecular and cellular programs underlying therapeutic response in RMC and nominate actionable stress-adaptation and stromal-immune circuits as potential targets for future biomarker-guided combination strategies.

Personal Statement

My research focuses on understanding how intrinsic tumor programs and microenvironmental ecosystems shape therapeutic response and resistance in aggressive cancers. As a postdoctoral fellow at MD Anderson Cancer Center, I integrate multi-omic data to dissect cellular heterogeneity, lineage plasticity, proteotoxic stress responses, and stromal-immune interactions. In my current work on SMARCB1-deficient renal medullary carcinoma, I use high-resolution single-cell profiling to define immune and malignant cell states associated with response to ixazomib-based therapy, and to identify stress-adaptation circuits that drive resistance. Attending this conference will allow me to present these findings, receive feedback from leaders in tumor immunology and systems oncology, and build collaborative networks essential for translating mechanistic insights into biomarker-guided precision medicine. Exposure to cutting-edge approaches in single-cell analytics, tumor microenvironment biology, and therapeutic resistance will directly strengthen my ongoing research. My long-term goal is to lead an independent laboratory dedicated to mapping the tumor ecosystem at single-cell resolution, identifying predictive biomarkers of treatment response, and developing combination strategies that overcome resistance in cancers. I am committed to advancing translational cancer research that bridges computational modeling, multi-omic profiling, and therapeutic development to improve patient outcomes.

Proposed Work

Tumor metastasis is the major cause of death in kidney cancer patients. Dr. DeBerardinis and his team aim to identify the metabolic pathways required for metastasis. They developed techniques to compare metabolism between primary and metastatic kidney tumors in patients. The group previously observed that oxidative mitochondrial metabolism was activated in metastatic tumors. In mice, mitochondrial metabolism was necessary and sufficient to induce metastasis from the kidney.

In this project, Dr. DeBerardinis proposes to test the effect of ONC201, which blocks mitochondrial activity by activating the protease ClpP, on kidney cancer growth and metastasis in mice. He also proposes to use deuterium MRI (dMRI) to non-invasively assess  mitochondrial activity and assess the effect of ONC201 on these pathways.

Anticipated Impact

ONC201 is well-tolerated in patients, and dMRI can be used in humans. If successful, this study may lay the groundwork for future clinical trials in kidney cancer. 

“I am grateful for the 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 proposal will provide foundational data for imaging and therapeutic clinical trials in kidney cancer.”

Proposed Work

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.

Anticipated Impact

This work aims to explore whether combining ECM-targeted strategies with pharmacological interventions could offer therapeutic benefits and potentially improve treatment outcomes in high-risk Wilms tumors.

“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.”

Proposed Work

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’s team has developed a phenotypic screening strategy to identify small molecules that disrupt TFE3-chromatin interactions essential for oncogenesis. Screening of 25,000 compounds identified 62 hits, acting through two complementary mechanisms: retention/trapping of TFE3 on chromatin or displacement of TFE3 from chromatin.

Dr. Viswanathan will focus on further functional validation of these hits and mechanistic characterization via a suite of cell-based and biochemical deconvolution assays.

Anticipated Impact

This effort aims to establish a robust pipeline for screening for TFE3 inhibitors, which may enable future large-scale screens and enable the development of a first-in-class targeted therapy for tRCC.

“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 needs that currently lacks specifically approved therapies.”

Proposed Work

Human endogenousretroviral (HERV) antigens are thought to drive the unexpectedly high response of clear cell renal cell carcinoma (ccRCC) to immune checkpoint inhibitors, despite its low mutation and neoantigen burden. Dr. Warren and his team aimed to characterize 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.

Anticipated Impact

If successful, these studies may help lay the groundwork for a potential new approach to kidney cancer treatment, based on cellular therapy or vaccination.

“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.”

Proposed Work

Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is often associated with the inactivation of VHL protein, which leads to the stabilization and accumulation of HIF-2α protein. Although the HIF-2α inhibitor belzutifan has received FDA approval for the treatment of ccRCC patients, both intrinsic and adaptive resistance to this drug have been reported. Dr. Zhang sought to identify potential targetable pathways that may contribute to HIF-2α inhibitor resistance.

Project Findings

Dr. Zhang and his team identified PTGES as a context-dependent contributor to belzutifan resistance. This finding may help explain variable responses to HIF-2α inhibitors and highlight PTGES as a potential therapeutic target for a subset of patients.

“HIF-2α inhibitor Belzultifan 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 on uncovering the mechanisms underlying drug resistance and developing alternative treatments for HIF-2α inhibitor-resistant patients in kidney cancer.”

Background

Metastasis is the deadliest cancer stage, and there is no universal treatment. Different tumors have distinct tissue-specific signatures, but as cancer progresses, they follow a common evolutionary trajectory toward invasiveness and metastasis. Targeting this shared vulnerability in metastatic tumors holds significant translational potential. Recent insights from kidney cancer reveal a novel metastatic mechanism, leading to the discovery of small-molecule drugs, SIMs, that selectively inhibit metastasis across cancers. By understanding SIMs, we aimed to create safer, more effective treatments, potentially saving over 500,000 lives annually in the U.S.

Method & Results

1) New concept: Metastasis requires cooperation between VHL+ and VHL- cells, with VHL- cells driving growth and migration in VHL+ cells.

2) SIM candidates: In high-throughput screening of 2,530 FDA-approved drugs, drugs selectively inhibiting VHL cells were identified, with fluvastatin being the most potent (“SIM-1”). Subsequent SAR studies identified SIM-2, four times more potent than fluvastatin (IC₅₀ 92nM).

3) Older statins (fluvastatin, simvastatin) were more cytotoxic than newer statins (e.g., atorvastatin and rosuvastatin) despite a lower affinity for their known target, HMG-CoA reductase (HMGCR). Thus, SIMs target a pathway distinct from cholesterol-lowering or HMGCR.

4) Transcriptomics and proteomics analyses suggest that older statins may target a non-HMGCR molecule in their anti-metastatic activities, possibly explaining mixed clinical trial results regarding statin use as antineoplastics.

5) SIMs are effective in treating various cancers, including kidney, breast (TNBC), and prostate (NEPC).

Conclusions

Critical steps to advancing SIM development toward clinical translation are (i) target identification and (ii) target and therapeutic validation. While our focus is on metastatic renal cell carcinoma (mRCC) to identify SIM’s drug target, strategic findings from this project will be directly relevant to other high-risk urological cancers. By investigating this further, we could develop a novel pan-cancer anti-metastatic drug.

Personal Statement

Cancer research has advanced significantly, revealing new vulnerabilities in cancer cells and developing new treatments such as immune checkpoint inhibitors. However, it’s still far away from curative therapy, especially against metastatic diseases. That is why I am here at UCLA Pharmacology, investigating the metastatic mechanism with a focus on heterogeneity. The primary goal of my project is to develop a new drug that can target intratumoral communication that drives distant metastases. Our effort has led to promising discoveries, such as statins’ selective toxicity against the metastatic driver. This is especially exciting because 1) statins are already FDA-approved and widely used in the clinic, but 2) their mechanism of action, as well as indications for metastatic diseases, are unknown. I am so eager to share these findings at the AACR Annual Meeting with world-renowned scientists in the field to gain valuable feedback and potentially facilitate new collaborations that could further propel this project. My long-term career aspirations include becoming a scientific expert on metastatic cancer who also understands the business side of biotech. The more I know about the drug development process, the more I realize the importance of having well-strategized financial and IP plans. To maximize the commercial potential of academic research, I will put myself on both sides of the world and bridge the two so that biotech continues to flourish for the better future of patients.

Research Summary

Clear cell renal cell carcinoma (ccRCC) is the most common malignancy originated from the kidney, with bone and lungs as the main sites of distant spread in vast majority of patients. A key feature of ccRCC is the loss of function of the von Hippel-Lindau (VHL) protein leading to enhanced angiogenesis; in addition, ccRCC exhibits a rich and heterogeneous immune infiltrate. Consequently, different anti-angiogenic tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)have emerged as standard of care for these patients, as single agents or in combination. Yet, limited data are available ontheir efficacy in different metastatic sites, and their impact on the immune infiltrate is unclear. We hypothesized thatmodulation of the microenvironment with a TKI provides an additive impact on ICI, and the outcome of combinational treatments depends on metastatic sites, treatment doses and tumor size.To this purpose, we implanted a luciferase-GFP-positive RENCA-VHL- cell line in the tibia of immunocompetent mice, resulting in synchronous bone and lung metastases. Cabozantinib (C), as one of the most potent TKIs, anti-programmed celldeath protein 1 (Anti-PD1) and anti-CTLA4 antibodies, were used as single agents or in combination. The outcomes weremonitored by macroscopic bioluminescence detection in vivo, and 3D multiparametric spatial analysis of bones and lungs, ex vivo. Compared to control-treated mice, all agents significantly reduced tumor progression at both tumor sites. Although all these treatments are clinically applied at stage IV of disease development, differences in their efficacy were noted once treatment was withdrawn. Spatial analysis of tumor cells, immune infiltrate and blood vessels revealed significant changes dependent on treatment, tumor site and time, with potential synergistic mechanism by TKIs when used in combination with ICI. We proved the efficacy of standard of care for bone and lung lesions of ccRCC in an immunocompetent mouse model and identified differences between treatments at the cellular level in the tumor microenvironment. We believe our studies may provide important insights and efficacy predictions for therapeutic applications in metastatic ccRCC patients.

Personal Statement

The most commonly applied drugs for metastatic kidney cancer, antiangiogenic tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI), have not been specifically studied in any metastatic site.

Hence, there is no data about determinants of response or resistance in these tumor niches. Up to date, nobody has defined the biology of clear cell renal cell carcinoma in bone or lungs, neither the role of the immune infiltrate nor its changes by treatment. Therefore, I developed first immunocompetent mouse model with these two metastatic sites in order to study standard of care and their influence on tissue microenvironment. By attending AACR25 I would broaden my prospective on spatial biology and learn how to apply current knowledge and techniques to level up our research. As a physician, I strongly believe that the future of oncology and medicine relies on physicians who can translate highly relevant clinical questions to the lab bench and contribute to unmet needs in curing cancer. Therefore, as a fourth-year postgraduate fellow while applying for medical residency programs to become physician-scientis, my end goal is to dedicate my lifetime to bone metastases in genitourinary malignancies and patients affected with this unfavorable course of cancer. I am convinced that nothing of these would have sense if we do not share our knowledge among scientists from the rest of the world at the conferences like AACR25.

Research Summary

Renal medullary carcinoma (RMC) is defined by the loss of the SMARCB1 tumor suppressor and represents one of the most aggressive kidney cancers, predominantly affecting young individuals of African descent with the sickle cell trait. RMC exhibits rapid progression, and poor response to standard therapies, with a median survival of only 13 months following diagnosis. In pursuit of more effective treatments, we launched two clinical trials specifically for patients with RMC evaluating anti-PD1 + anti-CTLA4 immune checkpoint therapy (ICT) with nivolumab + ipilimumab (ClinicalTrials.gov identifier: NCT03274258) and anti-PD1 + anti-LAG3 ICT using nivolumab + relatlimab (ClinicalTrials.gov identifier: NCT05347212). However, both trials were terminated early for futility due to resistance and hyperprogression by the established consensus Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 radiological criteria in Matos et al. Clin Cancer Res. 2020 (PMID: 31757877). Co-clinical experiments testing the same ICT regimens in our immunocompetent somatic mosaic genetically engineered mouse model (GEMM) of RMC demonstrated similar patterns of resistance and hyperprogression with ICT compared with IgG control. The combination of anti-PD1 with either anti-CTLA4 or anti-LAG3 significantly accelerated primary tumor progression and markedly increased metastatic burdens in the lung and liver of RMC mice. Comprehensive analyses, including longitudinally collected single-cell RNA sequencing from human RMC patient samples and RNA sequencing of GEMM RMC tumors revealed significant transcriptional reprogramming, enhanced tumor proliferation, activation of oncogenic pathways, and a shift toward myeloid-specific gene expression by RMC tumor cells in response to ICT. In our RMC mouse models, tumor cells have been engineered to express green fluorescent protein (GFP), enabling us to distinguish them from non-malignant mouse cells. Accordingly, multiplex immunofluorescence (mIF) revealed that tumor tissues from mice treated with ICT showed a significant increase of tumor cells co-expressing GFP and myeloid markers such as CD68, F4/80 and S100A9. Differential patterns of resistance and hyperprogression when RMC mice were treated with monotherapies targeting PD1, CTLA4, or LAG3. To counteract ICT-induced hyperprogression, we tested the CEBPB/p300 complex inhibitor IACS16898 which successfully induced tumor responses when combined with ICT in our RMC GEMM. IACS16898 treatment significantly reduced the expression of myeloid-associated markers on GFP+ tumor cells. Our study not only elucidates a novel mechanism of resistance and hyperprogression to PD1 plus either CTLA4 or LAG3 inhibition in SMARCB1-deficient cancers but also provides a foundation for targeting oncogenic and resistance pathways in RMC treated with distinct immunotherapy regimens. 

Personal Statement

My long-term research interests focus on identifying novel therapeutic targets for aggressive cancers with limited treatment options. Losing a close family member to lymphoma at a young age fueled my passion to pursue cancer research. As a medical doctor with a Ph.D. in cancer biology, I bring a unique perspective to addressing clinical needs through basic research. My Ph.D. work under Dr. Powel Brown at MD Anderson focused on triple-negative breast cancer (TNBC), where I identified NUDT5 as a phosphatase that maintains TNBC growth by preventing oxidative DNA damage. I demonstrated the efficacy of a NUDT5 inhibitor in suppressing tumor growth, leading to a first-author publication in Breast Cancer Research and presentations at prestigious conferences like the San Antonio Breast Cancer Symposium. My postdoctoral research builds on this foundation, addressing immunotherapy resistance in renal medullary carcinoma (RMC), a rare, aggressive kidney cancer affecting young individuals. My work has already contributed to a manuscript under revision Nature Cancer. My goal is to become a physician-scientist who bridges patient care and research, addressing real-life challenges in oncology. Attending the AACR meeting will provide an invaluable platform to present my findings, gain expert feedback, and foster collaborations to advance cancer treatment. The AACR Scholar-in-Training Award will help me further my mission to develop effective therapies for aggressive cancers.