What type of study is this?

This is a Observational study (also classified as: Drug Screening, Sequencing).

September 10, 2025

Abstract P03: Comprehensive Molecular Characterization of Collecting Duct Carcinoma for Therapeutic Vulnerability

PGPeiyong GuanAgency for Science, Technology and Research JCJianfeng ChenSun Yat-sen University CMChengqiang MoSun Yat-sen University

Key Points

KRAS hotspot mutations were identified in 23% of patients with collecting duct carcinoma, indicating potential genetic targets.
Analysis of 13 patients revealed significant molecular alterations, including mutations in TP53 and NF2.
Drug screening identified a CDK9 inhibitor that significantly inhibited tumor growth in newly established preclinical models.
Cell cycle-related pathways emerged as the most dysregulated, suggesting novel therapeutic approaches for treatment.

Abstract

Abstract Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer. Citation Format: Peiyong Guan, Jianfeng Chen, Chengqiang Mo, Fukawa Tomoya, Chao Zhang, Xiuyu Cai, Mei Li, Jing Han Hong, Jason Yongsheng Chan, Cedric Chuan Young Ng, Jing Yi Lee, Suet Far Wong, Wei Liu, Xian Zeng, Peili Wang, Rong Xiao, Vikneswari Rajasegaran, Swe Swe Myint, Abner Ming Sun Lim, Joe Poh Sheng Yeong, Puay Hoon Tan, Choon Kiat Ong, Tao Xu, Yiqing Du, Fan Bai, Xin Yao, Bin Tean Teh, Jing Tan. Comprehensive Molecular Characterization of Collecting Duct Carcinoma for Therapeutic Vulnerability abstract. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85 (15Suppl): Abstract nr P03.

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