Selective inhibition of ALDH1A3 impedes breast cancer growth and metastasis by blocking ALDH1A3-driven transcriptional programs

iScience 2026 Open access

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Authors: Maya R. MacLean, Bianca Laura Bernardoni, Wasundara Fernando, Giovanni Petrarolo, Ilaria D’Agostino, Cheryl A. Dean, Jaganathan Venkatesh, Christopher S. Hughes, Kerry B. Goralski, Geetha Subramanian, Raj Pranap Arun, Hannah F. Cahill
+5 more Olivia L. Walker, Lynn N. Thomas, Robert C. Douglas, Concettina La Motta, Paola Marcato
DOI: 10.1016/j.isci.2026.114863
Cited by: 3
References: 90

Abstract

, significantly reduces only ALDH1A3-dependent tumor growth and lung metastasis in TNBC xenografts. These effects are accompanied by selective inhibition of ALDH1A3 target genes in tumors, while pharmacokinetic studies demonstrate broad tissue distribution to metastatic sites, sustained target engagement, and favorable oral bioavailability. CLM296 shows no observable toxicity in preclinical models, supporting its potential as a first-in-class ALDH1A3 inhibitor for ALDH1A3-positive cancers.

Fields of Study & Subjects

Histone Deacetylase Inhibitors Research Alcohol Consumption and Health Effects Sphingolipid Metabolism and Signaling

Publication details

Journal / source
iScience
Publisher
Elsevier BV
Volume
29
Issue
3
Pages
114863–114863
Publication date
31 January 2026
Language
EN