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HDAC6 as a Prognostic Factor and Druggable Target in HER2-Positive Breast Cancer
Michela Cortesi1, Sara Bravaccini1, Sara Ravaioli1
1IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Cancers
|November 27, 2024
Summary
This study identifies HDAC6 as a predictor of recurrence in HER2+ breast cancer (BC) patients treated with trastuzumab. Combining HDAC6 inhibitors with trastuzumab shows promise for overcoming drug resistance in BC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Adjuvant trastuzumab is standard for HER2+ breast cancer (BC).
- Over 50% of patients develop resistance to trastuzumab.
- Identifying molecular factors for relapse is crucial for new therapeutic strategies.
Purpose of the Study:
- Identify molecular factors associated with disease relapse in HER2+ BC patients.
- Investigate these factors as potential therapeutic targets.
Main Methods:
- Analyzed tumor tissues from relapsed and non-relapsed HER2+ BC patients.
- Utilized nCounter Human Breast Cancer Panel 360 for gene expression analysis.
- Employed logistic regression and network pharmacology to identify recurrence-associated genes and drug efficacy.
Main Results:
- Higher HDAC6 expression correlated with increased recurrence risk (OR=3.20, p=0.016).
- HDAC6 inhibitor Nexturastat A (NextA) combined with trastuzumab demonstrated synergistic effects on trastuzumab-resistant HER2+ BC cell lines.
- HSP90AA1 was identified as a potential mediator of this synergism.
Conclusions:
- HDAC6 shows potential as a prognostic factor in HER2+ BC.
- Combination therapy with HDAC6 inhibitors and trastuzumab warrants further investigation for overcoming resistance in HER2+ BC patients.
