Fractionated follow-up chemotherapy delays the onset of resistance in bone metastatic prostate cancer
type: Item
instance of: scholarly article
title: Fractionated follow-up chemotherapy delays the onset of resistance in bone metastatic prostate cancer
zbMATH Open document ID: 1395.92089
author: Pranav I. Warman
author: Artem Kaznatcheev
author: Arturo Araujo
author: Conor C. Lynch
author: D. Basanta
published in: Games
publication date: 2018-07-10T00:00:00Z
review text: Summary: Prostate cancer to bone metastases are almost always lethal. This results from the ability of metastatic prostate cancer cells to co-opt bone remodeling, leading to what is known as the \textit{vicious cycle}. Understanding how tumor cells can disrupt bone homeostasis through their interactions with the stroma and how metastatic tumors respond to treatment is key to the development of new treatments for what remains an incurable disease. Here we describe an evolutionary game theoretical model of both the homeostatic bone remodeling and its co-option by prostate cancer metastases. This model extends past the evolutionary aspects typically considered in game theoretical models by also including ecological factors such as the physical microenvironment of the bone. Our model recapitulates the current paradigm of the ``vicious cycle'' driving tumor growth and sheds light on the interactions of heterogeneous tumor cells with the bone microenvironment and treatment response. Our results show that resistant populations naturally become dominant in the metastases under conventional cytotoxic treatment and that novel schedules could be used to better control the tumor and the associated bone disease compared to the current standard of care. Specifically, we introduce fractionated follow up therapy -- chemotherapy where dosage is administered initially in one solid block followed by alternating smaller doses and holidays -- and argue that it is better than either a continuous application or a periodic one. Furthermore, we also show that different regimens of chemotherapy can lead to different amounts of pathological bone that are known to correlate with poor quality of life for bone metastatic prostate cancer patients.
Mathematics Subject Classification ID: 92C50
Mathematics Subject Classification ID: 91A22
zbMATH DE Number: 6901029
zbMATH Keywords: evolutionary game theory
zbMATH Keywords: prostate cancer bone metastasis
zbMATH Keywords: chemotherapy
zbMATH Keywords: heterogeneity
zbMATH Keywords: resistance
MaRDI profile type: Publication
full work available at URL: g9020019
OpenAlex ID: W2794823324
cites work: Modelling the anabolic response of bone using a cell population model
cites work: Studying the emergence of invasiveness in tumours using game theory
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cites work: Spatial evolutionary games with weak selection
DOI: 10.3390/G9020019
description: scientific article; zbMATH DE number 6901029