Work

Epigenetic dysregulation of HOX genes in breast cancer and emerging therapeutic strategies

Year: 2026

Type: article

Abstract: Homeobox ( HOX ) genes encode evolutionarily conserved transcription factors that govern developmental identity and differentiation. In breast cancer, HOX dysregulation is bidirectional and context dependent rather than uniformly oncogenic: HOXA2 , HOXA5 , and HOXC8 show tumor-suppressive or differentiation-associated functions, whereas HOXB7 , HOXB9 , HOXB13 , and HOXC10 are linked to progression or treatment resistance in defined settings. This review critically integrates evidence from human tumors and clinical cohorts with mechanistic findings from cell and animal models. Beyond effects on proliferation, apoptosis, epithelial-mesenchymal transition, invasion, and angiogenesis, HOX networks may influence lineage state, stem-like phenotypes, cellular plasticity, and therapy adaptation. We propose that apparently paradoxical HOX functions can be understood through interactions among PBX/MEIS cofactors, chromatin accessibility, signaling context, and post-translational regulation. Particular attention is given to subtype-associated patterns, the clinically translated HOXB13 :IL17BR component of the Breast Cancer Index, and therapy-driven tumor evolution. Direct HOX -targeted strategies-including HOX-PBX inhibitors, RNA-based approaches, epigenetic modulation, and dependency-guided combination strategies-remain preclinical in breast cancer. Major barriers include functional redundancy, delivery and pharmacokinetic limitations, patient selection, and potential on-target/off-tumor effects in normal stem and progenitor compartments. Future longitudinal, single-cell, spatial, epigenomic, and functional-genomic studies should determine which HOX alterations are drivers, biomarkers of cell state, or therapeutically exploitable dependencies.

Source: Discover Oncology

DOI: 10.1007/s12672-026-06203-6

Authors: Buddha Sai Keerthana, Pangi Vijaya Nirmala, Alavala Matta Reddy, Abhinash Marukurti, L. Pradeepthi Pemmaraju, Shaik Farhana

Institution: Adikavi Nannaya University

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,690