Abiraterone-Docetaxel scheduling for metastatic castration-resistant prostate cancer based on evolutionary dynamics

Sep 24, 2026

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Patients with metastatic castration-resistant prostate cancer (mCRPC) are categorized into best responder, responder, and non-responder groups according to their response to abiraterone. In the responder and non-responder groups, treatment can fail as drug-resistant cells emerge within the tumor environment. The paper suggests using a secondary drug to suppress drug-resistant subpopulations and prolong disease inhibition. It proposes combination docetaxel and abiraterone schedules within polytherapy strategies, using Evolutionary Game Theory for mathematical modeling.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Abstract

Introduction

PLOS ONE OPEN ACCESS Citation: Deris A, Sohrabi-Haghighat M (2023) Abiraterone-Docetaxel scheduling for metastatic castration-resistant prostate cancer based on evolutionary dynamics. PLoS ONE 18(3): e0282646 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pone.0282646 Editor: Onder Tutsoy, Adana Alparslan Turkes Science and Technology University: Adana Alparslan Turkes Bilim ve Teknoloji Universitesi, TURKEY Received: November 25, 2021 Accepted: February 20, 2023 Published: March 9, 2023 Copyright: © 2023 Deris, Sohrabi-Haghighat. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting information files. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. RESEARCH ARTICLE Abiraterone-Docetaxel scheduling for metastatic castration-resistant prostate cancer based on evolutionary dynamics Atefeh Deris☯, Mahdi Sohrabi-Haghighat *☯ Faculty of Science, Arak University, Arak, Iran ☯ These authors contributed equally to this work. * [m-haghighat@araku.ac.ir](m-haghighat@araku.ac.ir) Abstract Patients with metastatic castration-resistant prostate cancer (mCRPC) are divided into three groups based on their response to Abiraterone treatment: best responder, responder, and non-responder. In the latter two groups, successful outcomes may not be achieved due to the development of drug-resistant cells in the tumor environment during treatment. To overcome this challenge, a secondary drug can be used to control the population of drugresistant cells, potentially leading to a longer period of disease inhibition. This paper proposes using a combination of Docetaxel and Abiraterone in some polytherapy methods to control both the overall cancer cell population and the drug-resistant subpopulation. To investigate the competition and evolution of mCRPC cancer phenotypes, as in previous studies, the Evolutionary Game Theory (EGT) has been used as a mathematical modeling of evolutionary biology concepts. Introduction Prostate cancer is a common cancer among men and the second-leading cause of cancer death in men [ 1] . Early diagnosis is possible through Prostate-Specific Antigen (PSA) testing, improving men’s life expectancy [2] . High levels of androgens are associated with the development and progression of prostate cancer in men. CYP17A, AR, SRD5A2, HSD3B1, and HSD3B2 genes play a special role in androgen metabolism and cell proliferation in the prostate [3] . Androgen deprivation therapy (ADT) is used to slow the growth of prostate cancer by reducing the androgen concentration in blood or preventing androgens from affecting the prostate cancer cells [4] . The CYP17A enzyme is involved in androgen synthesis and the pathogenesis of prostate cancer. Inhibitors of CYP17A, such as abiraterone, stop the production of androgens by prostate cancer cells by inhibiting the CYP17A enzyme in the prostate [5, 6] . Metastatic castration-resistant prostate cancer can still grow and spread despite reduced testosterone production [7, 8] . There are three phenotypes of mCRPC: T+, TP, and T− . T+ cells require testosterone to survive and multiply, while TP cells produce the necessary testosterone through rearrangement of CYP17A. T− cells, which are resistant, can multiply without relying on testosterone [9, 10] . One common treatment for mCRPC is the use of maximum tolerated dose (MTD) treatment, in which medications are used at their highest tolerable dose as long as there are no side effects. However, the MTD treatment approach can lead to the elimination of sensitive phenotypes and the competitive release of the resistant population

FAQs

How are mCRPC patients grouped based on response to abiraterone?

They are divided into best responder, responder, and non-responder groups according to treatment response to abiraterone.

Why can treatment fail in the responder and non-responder groups?

Because drug-resistant cells can develop in the tumor environment during treatment, preventing successful outcomes.

What modeling framework is used to study competition and evolution of mCRPC phenotypes?

Evolutionary Game Theory (EGT) is used as a mathematical modeling approach to represent evolutionary biology concepts and phenotype competition.

Sep 24, 2026

Uploaded by moss~