Faculty, Staff and Student Publications

Publication Date

11-18-2025

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2025.102423

PMID

41172996

PMCID

PMC12711661

PubMedCentral® Posted Date

10-30-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Renal medullary carcinoma (RMC) is a rare but highly aggressive kidney cancer that resists conventional therapies. To identify therapeutic targets, this study employs histopathologic, genomic, and transcriptomic profiling of 25 RMC samples. TROP2, EPCAM, CLDN6, and CDH6 are significantly overexpressed compared with other renal and solid tumors. Pathway analyses indicate Hippo pathway upregulation and a tumor microenvironment rich in fibroblasts and neutrophils. We subsequently explore treatment of four heavily pretreated patients, all with high TROP2 expression, using sacituzumab govitecan, a TROP2-targeted antibody-drug conjugate. Of these four patients, one patient achieves a partial response with symptom improvement, two patients maintain stable disease, and the median progression-free survival reaches 2.9 months. This study represents the most extensive molecular characterization of RMC to date, identifying TROP2 and other potential therapeutic targets. Sacituzumab govitecan demonstrates potential clinical benefit, warranting further evaluation in prospective trials to confirm its efficacy and explore additional targets identified herein.

Keywords

Humans, Kidney Neoplasms, Gene Expression Profiling, Male, Female, Middle Aged, Antigens, Neoplasm, Genomics, Aged, Carcinoma, Renal Cell, Transcriptome, Gene Expression Regulation, Neoplastic, Antibodies, Monoclonal, Humanized, Carcinoma, Medullary, Tumor Microenvironment, Cell Adhesion Molecules, CLDN6, CDH6, EPCAM, Hippo pathway, renal medullary carcinoma, sacituzumab govitecan, SMARCB1, TROP2

Published Open-Access

yes

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