Fibroblasts and alectinib switch the evolutionary games played by non-small cell lung cancer

Kaznatcheev, Artem; Peacock, Jeffrey; Basanta, David; Marusyk, Andriy; Scott, Jacob G.

doi:10.1038/s41559-018-0768-z

Cited by 131 publications

(202 citation statements)

References 40 publications

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“…Bacevic et al [12] make similar observations for CDKi resistant cells and a number of further examples can be found in the literature (e.g. [19,20,21,22,23]). In their original work on adaptive therapy, Gatenby et al [2,3] used the cost of resistance to motivate adaptive therapy, and most theoretical studies since have made this assumption [12,13,14].…”

Section: Introductionmentioning

confidence: 64%

Turnover modulates the need for a cost of resistance in adaptive therapy

Strobl

West

Viossat

et al. 2020

Preprint

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Control and conquer" -this is the philosophy behind adaptive therapy, which seeks to exploit intra-tumoural competition to avoid, or at least, delay the emergence of therapy resistance in cancer. Motivated by promising results from theoretical, experimental and, most recently, a clinical study in prostate cancer, there is an increasing interest in extending this approach to other cancers. As such, it is urgent to understand the characteristics of a cancer which determine whether it will respond well to adaptive therapy, or not. A plausible candidate for such a selection criterion is the fitness cost of resistance. In this 1 paper, we study a simple competition model between sensitive & resistant cell populations to investigate whether the presence of a cost is a necessary condition for adaptive therapy to extend the time to progression beyond that of a standard-of-care continuous therapy. We find that for tumours close to their environmental carrying capacity such a cost of resistance is not required. However, for tumours growing far from carrying capacity, a cost may be required to see meaningful gains. Notably, we show that in such cases it is important to consider the cell turnover in the tumour and we discuss its role in modulating the impact of a cost of resistance. Overall, our work helps to clarify under which circumstances adaptive therapy may be beneficial, and suggests that turnover may play an unexpectedly important role in the decision making process.

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Section: Introductionmentioning

confidence: 64%

Turnover modulates the need for a cost of resistance in adaptive therapy

Strobl

West

Viossat

et al. 2020

Preprint

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“…(such as the 1mL proposed by Toprak and colleagues) can be specified so that the about the interactions of the different species/types of bacteria [27,28].…”

mentioning

confidence: 99%

A low-cost, open-source evolutionary bioreactor and its educational use

Gopalakrishnan

Krishnan

McClure

et al. 2019

Preprint

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Recently, a concerted effort has been made to study the evolution of drug resistance in organisms at increasingly smaller time scales and in a high-throughput manner. One effective approach is through the use of customized bioreactors -devices that can continuously culture bacteria and monitor this growth in real time. These devices can be technically challenging and expensive to implement for scientists, let alone students or teachers who seek an innovative and intuitive way of studying evolution. We seek to provide a flexible and open source automated continuous culture device framework for the academic setting to study biological concepts such as population dynamics and evolution; a framework that is capable of replicating the functionality of many prominent and expensive bioreactors in the market today. Within the educational environment, our goal is to foster interaction and interest between the engineering and biological fields by allowing teachers and students to build their own systems and design experiments on the proposed open framework. We present a continuous culture device October 10, 2019 1/25 designed for bacterial culture that is easily and inexpensively constructed, lends itself to evolution experiments, and can be used both in the academic and educational environments. Author summaryThe continuous monitoring of population growth in the presence of cytotoxic selective pressures can reveal new insights into resistance development and corresponding susceptibilities. Bioreactors have been proposed to accomplish this task yet are costly and without formal build instructions or software. In this article, we present a framework for a bioreactor, called the EVolutionary biorEactor (EVE), that will enable users to economically implement hardware and create circuits through diagrams.Hardware communicates with open-source software, written in Python, to create a flexible yet fully featured bioreactor that incorporates many modes of operation. A single EVE controls many Culture Units simultaneously, each with the capability of running its own experiment or a replicate of the same experiment to measure stochastic differences during evolution. While currently built for bacterial culture, this framework can be adapted in many ways from continuous mammalian cell culture to the measurement of multi-population dynamics in various environments. In the educational setting, this easy-to-implement framework will enable educators to use a hands-on approach to evolution in their lessons and extracurricular activities. For scientists, we propose this open framework as a tool that can be used and modified to investigate new areas in population dynamics and evolution. Introduction 1Continuous microbial culture is a powerful tool for observing and directing evolution in 2 both research and industrial settings. Recently a shift towards open-source science has 3 brought about a new wave of Do-It-Yourself, customized continuous culture devices to 4 accommodate a wide variety of experimental designs across several research are...

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“…The present study suggests that intermittent rather than continuous chemotherapy may result in better outcomes in lung cancer. As far as we are aware, such an approach, although investigated in some other solid tumors (Cunningham et al, 2015; Zhang et al, 2017), has never been looked into in lung cancer although, the observations by Kaznatcheev et al (2019) are inferred to support the concept that treatment influences the character of the resistance response in cancer cells (Staňková K, 2019). Such a treatment approach may not cure the patient of the disease, but it would at least result in stable disease that can be managed while sparing the patient of undesirable effects of excessive chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have applied evolutionary game theory to cancer(Wu et al, 2014; Wu et al, 2015; Zhang et al, 2017; You et al, 2017; Swierniak et al, 2018; Kareva and Karev, 2019; Kaznatcheev et al, 2019; Stanková et al, 2019; West et al, 2019) but as far as we are aware, the adaptive strategies that drug naïve and drug tolerant or resistant NSCLC cancer cells adopt in response to environmental perturbations have not been investigated. A recent paper byKaznatcheev et al (2019) is the only other study where the authors developed an assay to measure effective evolutionary games in co-cultures of isogenic NSCLC cells that are sensitive and resistant to the anaplastic lymphoma kinase inhibitor alectinib. In contrast, in the present study we investigated a broad spectrum chemotherapy (cisplatin) and naturally occurring cisplatin-sensitive and tolerant NSCLC cell lines and developed the PSMSR model to model the experimental observations.…”

mentioning

confidence: 99%

Suppressing chemoresistance in lung cancer via dynamic phenotypic switching and intermittent therapy

A¹,

Mohanty²,

Bhattacharya

et al. 2020

Preprint

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A major challenge in cancer therapy is drug resistance, which is typically attributed to acquired mutations and tumor heterogeneity. However, emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance, although, the details of such mechanisms are poorly understood. Here, by combining real time cellular growth data with mathematical modeling, we showed that the cisplatinsensitive and tolerant lung cancer cells when co-cultured in cisplatin-free and cisplatintreated environments, exhibit drastically different group strategies in response to environmental changes. While tolerant cells exhibited a persister-like behaviour and were attenuated by sensitive cells, sensitive cells 'learned' to evade chemotherapy from tolerant cells when co-cultured. Further, tolerant cells could switch phenotypes to become sensitive, although high cisplatin concentrations suppressed this switching. Finally, switching cisplatin administration from continuous to intermittent suppressed the emergence of tolerant cells, suggesting that intermittent rather than continuous chemotherapy may result in better outcomes in lung cancer.

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Fibroblasts and alectinib switch the evolutionary games played by non-small cell lung cancer

Cited by 131 publications

References 40 publications

Turnover modulates the need for a cost of resistance in adaptive therapy

Turnover modulates the need for a cost of resistance in adaptive therapy

A low-cost, open-source evolutionary bioreactor and its educational use

Suppressing chemoresistance in lung cancer via dynamic phenotypic switching and intermittent therapy

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