A stochastic population model for the impact of cancer cell dormancy on therapy success

• Published in: Journal of theoretical biology Vol. 597; p. 111995
• Main Authors: Blath, Jochen, Kraut, Anna, Paul, Tobias, Tóbiás, András
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21.01.2025
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer cell dormancy; Computer Simulation; Humans; Individual-based models; Models, Biological; Multi-drug treatment; Neoplasms - drug therapy; Neoplasms - pathology; Neoplasms - therapy; Stochastic population dynamics; Stochastic Processes; Therapy evasion; Treatment Outcome; Treatment protocol design; Treatment success; Individual-based models; Multi-drug treatment; 60J85; Stochastic population dynamics; 92D25; Therapy evasion; Treatment protocol design; 34C60; Cancer cell dormancy; 92C50; Treatment success
• ISSN: 0022-5193; 1095-8541; 1095-8541
• DOI: 10.1016/j.jtbi.2024.111995

Therapy evasion – and subsequent disease progression – is a major challenge in current oncology. An important role in this context seems to be played by various forms of cancer cell dormancy. For example, therapy-induced dormancy, over short timescales, can create serious obstacles to aggressive treatment approaches such as chemotherapy, and long-term dormancy may lead to relapses and metastases even many years after an initially successful treatment. In this paper, we focus on individual cancer cells switching into and out of a dormant state both spontaneously as well as in response to treatment. We introduce an idealized mathematical model, based on stochastic agent-based interactions, for the dynamics of cancer cell populations involving individual short-term dormancy, and allow for a range of (multi-drug) therapy protocols. Our analysis – based on simulations of the many-particle limit – shows that in our model, depending on the specific underlying dormancy mechanism, even a small initial population (of explicitly quantifiable size) of dormant cells can lead to therapy failure under classical single-drug treatments that would successfully eradicate the tumour in the absence of dormancy. We further investigate and quantify the effectiveness of several multi-drug regimes (manipulating dormant cancer cells in specific ways, including increasing or decreasing resuscitation rates or targeting dormant cells directly). Relying on quantitative results for concrete simulation parameters, we provide some general basic rules for the design of (multi-)drug treatment protocols depending on the types and processes of dormancy mechanisms present in the population. •We define a stochastic agent-based model for cancer cell dormancy and chemotherapy.•The main subject of our simulation study is the ODE system arising from this model.•Even a small fraction of dormant cancer cells can prevent treatment success.•We analyse several multidrug regimes, targeting also dormant cells in different ways.•Depending on the parameters, we provide basic rules for treatment protocol design.