Gut microbiota and its metabolites - Key factors of drug resistance in the treatment of advanced prostate cancer (Review)

Sep 23, 2026

Uploaded by Rizky

Prostate cancer is a major cause of cancer-related death in men, with rising global incidence. Standard therapies for advanced disease include androgen deprivation therapy, surgery, radiotherapy, chemotherapy, and immunotherapy, yet drug-based treatment commonly results in the development of drug resistance. This review summarizes how gut microbiota and their metabolites contribute to treatment resistance in advanced prostate cancer, highlights microbiome-targeted therapeutic possibilities, and outlines future research directions to support new strategies and improve prognosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

introduction

Gut microbiota and treatment resistance

current status of Pca treatment resistance

Mechanisms of gut microbiota in Pca treatment resistance

Potential therapeutic strategies

challenges and future perspectives

conclusion

Molecular Medicine rePorTS 34: 190, 2026 Gut microbiota and its metabolites: Key factors of drug resistance in the treatment of advanced prostate cancer (Review) JinGHenG SonG1* , HonGGuo cui 1* , PeiSen YanG1* , YanKai Xu1 , YuanYuan liu 1 , GanG ZHanG1 , 1 1 1 2 1 YanGYanG liu , aiMin Tian , JiZHonG cHe , Hui Sun and ZHenGcHao ZHanG 1Urology Department, Yantai Affiliated Hospital of Binzhou Medical University, The Second Clinical Medical College of Binzhou Medical university, Yantai, Shandong 264100, P.r. china; 2research and Translational center for immunological disorders, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China received december 22, 2025; accepted april 7, 2026 doi: 10. 3892/mmr.2026.13900 Abstract. Prostate cancer (Pca) is a leading cause of cancer‑related deaths among men, and its incidence is increasing worldwide. current treatments include androgen deprivation therapy, surgery, radiotherapy, chemotherapy and immunotherapy, among others. Surgical treatment has a less effective therapeutic effect in patients with advanced Pca . However, drug‑based treatments often lead to the development of drug resistance, highlighting the need to adopt new treat‑ ment strategies. The present review summarizes the role of gut microbiota and its metabolites in the treatment resistance of advanced Pca, potential microbiome‑targeted therapies and future research directions, for developing novel thera‑ peutic approaches to overcome drug resistance and improve prognosis. Contents 1. introduction 2. Gut microbiota and treatment resistance 3. current status of Pca treatment resistance 4. Mechanisms of gut microbiota in Pca treatment resistance 5. Potential therapeutic strategies 6. challenges and future perspectives 7. conclusion 1. Introduction Prostate cancer (PCa) is a significant global health concern, with an estimated 1.4 million new cases and >375,000 asso‑ ciated mortalities annually in 2020 (1) . in the united States, Pca is the most commonly diagnosed cancer among men, with ~290,000 new cases and 35,000 mortalities reported Correspondence to: Professor Zhengchao Zhang, Urology Department, Yantai Affiliated Hospital of Binzhou Medical university, The Second clinical Medical college of Binzhou Medical University, 717 Jinbu Street, Muping, Yantai, Shandong 264100, P.r. china e‑[mail: byytfyzzc@163.com](mail: byytfyzzc@163.com) Professor Hui Sun, research and Translational center for immunological disorders, Yantai affiliated Hospital of Binzhou Medical University, 717 Jinbu Street, Muping, Yantai, Shandong 264100, P.r. china e‑mail: [yaohy04@126.com](yaohy04@126.com) *contributed equally Abbreviations: ABCB1, ATP‑binding cassette subfamily B member 1 (P‑glycoprotein); adT, androgen deprivation therapy; ahr, aryl hydrocarbon receptor; AKT, protein kinase B; AR, androgen receptor; arV7, androgen receptor splicing variant 7; aTM, ataxia telangiectasia‑mutated gene; aTr, ataxia telangiectasia and Rad3‑related protein; BCL2, B‑cell lymphoma 2; BRCA2, breast cancer susceptibility gene 2; caFs, cancer‑associated fibroblasts; CB2, cannabinoid receptor 2; CCL20, C‑C motif chemokine ligand 20; crPc, castration‑resistant prostate cancer; mcrPc, metastatic crPc; diM, 3,3'‑diindolylmethane; eMT, epithelial‑mesenchymal transition; FMT, fecal microbiota transplantation; FoS, fructooligosaccharides; FXr, farnesoid X receptor; GoS, galactooligosaccharides; Hdac, histone deacetylase; Hdc, histidine decarboxylase; HiF‑1α , hypoxia‑inducible factor‑1α; HMoX1, heme oxygenase‑1; i3c, indole‑3‑carbinol; JaK2, Janus kinase 2; lPc, lysophosphatidylcholine; lPcaT1, lysophosphatidylcholine acyltransferase 1; Maldi‑ToF/MS, matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry; MaPK, mitogen‑activated protein kinase; MdScs, myeloid‑derived suppressor cells; MiF, macrophage migration inhibitory factor; mTor, mammalian target of rapamycin;

FAQs

Why does advanced prostate cancer often develop drug resistance?

Drug-based treatments frequently lead to the emergence of drug resistance over time, even when therapies initially show clinical responses. This drives the need for alternative strategies to overcome resistance.

What role do gut microbiota and their metabolites play in treatment resistance?

Gut microbiota can influence cancer progression and treatment response through mechanisms such as drug metabolism, immune modulation, and metabolite production. These processes affect tumor biology and resistance development.

What does the review propose for future directions and therapies?

The review discusses potential microbiome-targeted therapeutic strategies and outlines challenges and future perspectives. The goal is to develop novel approaches that improve prognosis by addressing resistance mechanisms.

Sep 23, 2026

Uploaded by Rizky