Morgan, Richard ORCID: https://orcid.org/0000-0002-8721-4479, Simpson, Guy, Arunachalam, Einthavy and Pandha, Hardev (2026) Inhibition of HOX/PBX dimers as a potential therapeutic strategy in breast cancer subtypes including Triple Negative Breast Cancer. Current Issues in Molecular Biology, 48 (8).

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Abstract

Triple negative breast cancer (TNBC) continues to have a poor prognosis relative to other forms of this disease. Previous studies have shown that the HOX[M1.1] family of transcription factors generally show increased expression in breast cancer and may have a primarily pro-oncogenic role. In this study, we assessed the sensitivity of a range of TNBC-derived cell lines to an inhibitor of HOX protein function, HTL-001, which blocks the interaction between HOX proteins and the Pre-B-cell Leukaemia Homeobox (PBX) cofactor. The sensitivity of cell lines was measured by MTS viability assays, and gene expression by RT-qPCR. Combination studies were performed with epigenetic modifiers (5-azacytidine (5-aza), Trichostatin A (TSA)) and standard-of-care chemotherapeutic drugs including Paclitaxel. A mouse tumour flank model of MDA-MB-231 cells was used to assess response to HTL-001, paclitaxel, or combination therapy. All the cell lines exhibited high levels of HOX dysregulation compared to an immortalised line derived from normal breast cells, and greater sensitivity to HTL-001-induced apoptosis. Epigenetic changes have previously been shown to be key modulators of HOX expression and, correspondingly, we show that reversing epigenetic changes in these cell lines significantly alters HOX expression and generally reduces sensitivity to HTL-001. In addition, HTL-001 shows synergistic interactions with several established chemotherapeutic agents in vitro. We further demonstrate that HTL-001 can significantly reduce tumour growth in a mouse model of TNBC. Our findings indicate that HOX/PBX dimers are a potential therapeutic target in this cancer.

Item Type:	Article
Identifier:	10.3390/cimb48080800
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Keywords:	triple negative breast cancer; HOX; PBX; transcription factor; apoptosis
Subjects:	Natural sciences > Cell and molecular biology Medicine and health
Date Deposited:	18 Aug 2026
Dates:	Date Publication status 20 May 2026 Submitted 3 August 2026 Accepted 7 August 2026 Published
School, department or research centre:	School of Medicine and Biosciences
Keywords:	triple negative breast cancer; HOX; PBX; transcription factor; apoptosis
URI:	https://repository.uwl.ac.uk/id/eprint/15275

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