Unveiling the Molecular Landscape of FOXA1 Mutant Prostate Cancer - Insights and Prospects for Targeted Therapeutic Strategies

Sep 24, 2026

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Prostate cancer remains a major global health challenge, and Forkhead box A1 (FOXA1) mutations define distinctive oncogenic biology. Comprehensive in silico analysis of TCGA transcriptomic data was used to compare FOXA1 mutant and control groups, revealing 1525 differentially expressed genes mapped to eight intrinsic and six extrinsic signaling pathways. Intrinsic pathway findings were supported by RNA-seq from 22Rv1 cells in GEO123619, indicating complex tumor microenvironment effects. Druggable targets and repurposing candidates were identified, including KDM1A, MAOA, PDGFB, and HSP90AB1, with implications for targeted therapy development.

LanguageEnglish

CategoryHealthcare

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Pages19

Reading Time48 min

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Abstract

Introduction

Article Unveiling the Molecular Landscape of FOXA1 Mutant Prostate Cancer: Insights and Prospects for Targeted Therapeutic Strategies Kyung Won Hwang 1, Jae Won Yun 2 and Hong Sook Kim 1, * Citation: Hwang, K.W.; Yun, J.W.; Kim, H.S. Unveiling the Molecular Landscape of FOXA1 Mutant Prostate Cancer: Insights and Prospects for Targeted Therapeutic Strategies. Int. J. Mol. Sci. 2023, 24, 15823. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms242115823 Academic Editor: Pierre Tennstedt Received: 8 September 2023 Revised: 12 October 2023 Accepted: 24 October 2023 Published: 31 October 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea; [hgw7656@gmail.com](hgw7656@gmail.com) 2 Veterans Health Service Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea; [jwyunmd@gmail.com](jwyunmd@gmail.com) * [Correspondence: hong2kim2@gmail.com or hongkim@skku.edu](Correspondence: hong2kim2@gmail.com or hongkim@skku.edu) Abstract: Prostate cancer continues to pose a global health challenge as one of the most prevalent malignancies. Mutations of the Forkhead box A1 (FOXA1) gene have been linked to unique oncogenic features in prostate cancer. In this study, we aimed to unravel the intricate molecular characteristics of FOXA1 mutant prostate cancer through comprehensive in silico analysis of transcriptomic data from The Cancer Genome Atlas (TCGA) . A comparison between FOXA1 mutant and control groups unearthed 1525 differentially expressed genes (DEGs), which map to eight intrinsic and six extrinsic signaling pathways. Interestingly, the majority of intrinsic pathways, but not extrinsic pathways, were validated using RNA-seq data of 22Rv1 cells from the GEO123619 dataset, suggesting complex biology in the tumor microenvironment. As a result of our in silico research, we identiﬁed novel therapeutic targets and potential drug candidates for FOXA1 mutant prostate cancer. KDM1A, MAOA, PDGFB, and HSP90AB1 emerged as druggable candidate targets, as we found that they have approved drugs throughout the drug database CADDIE. Notably, as most of the approved drugs targeting MAOA and KDM1A were monoamine inhibitors used for mental illness or diabetes, we suggest they have a potential to cure FOXA1 mutant primary prostate cancer without lethal side effects. Keywords: FOXA1; prostate cancer; drug repurposing; gene expression; pathway analysis; gene–drug network 1. Introduction Prostate cancer is one of the most diagnosed cancers in men, and despite signiﬁcant advances in diagnosis and treatment, it remains a major cause of mortality from cancer in men globally [1] . One of the major challenges in managing prostate cancer is the heterogeneity of the disease driven by genetic alterations such as gene mutations and chromosomal rearrangement, leading to diverse clinical outcomes and responses to treatment [2] . Recent advances in genomic and molecular proﬁling technologies have led to a deeper insight of the mechanisms underlying prostate cancer development and progression, as well as the responses to various drugs [3–5] . It emphasizes the importance of precision medicine and targeted therapies that aim to tailor medical treatment to an individual's unique characteristics, which offers more effective and less toxic treatments than traditional chemotherapy [6–8] . The molecular landscape of prostate cancer is characterized by recurrent genomic alterations, includingthe fusion of ETS family genes such as ERG, ETV1, ETV4, or FLI1, and genetic mutations i

FAQs

What was the study’s main goal regarding FOXA1 mutant prostate cancer?

The study aimed to uncover the molecular characteristics of FOXA1 mutant prostate cancer and derive insights for targeted therapeutic strategies through comprehensive in silico analysis.

How were FOXA1 mutant and control groups compared, and what was found?

Transcriptomic data from TCGA were compared between FOXA1 mutant and control groups, identifying 1525 differentially expressed genes mapped to intrinsic and extrinsic signaling pathways.

Which potential therapeutic targets were highlighted as druggable candidates?

KDM1A, MAOA, PDGFB, and HSP90AB1 were identified as druggable candidate targets, and approved drugs linked to these targets were reported from the CADDIE drug database.

Sep 24, 2026

Uploaded by Bulrr