Can Environmental Manipulation Help Suppress Cancer? Non‐Linear Competition Among Tumor Cells in Periodically Changing Conditions

Abstract

It has been shown that the tumor population growth dynamics in a periodically varying environment can drastically differ from the one in a fixed environment. Thus, the environment of a tumor can potentially be manipulated to suppress cancer progression. Diverse evolutionary processes play vital roles in cancer progression and accordingly, understanding the interplay between these processes is essential in optimizing the treatment strategy. Somatic evolution and genetic instability result in intra‐tumor cell heterogeneity. Various models have been developed to analyze the interactions between different types of tumor cells. Here, models of density‐dependent interaction between different types of tumor cells under fast periodical environmental changes are examined. It is illustrated that tumor population densities, which vary on a slow time scale, are affected by fast environmental variations. Finally, the intriguing density‐dependent interactions in metastatic castration‐resistant prostate cancer (mCRPC) in which the different types of tumor cells are defined with respect to the production of and dependence on testosterone are discussed.

Nonlinear eco-evolutionary games with global environmental fluctuations and local environmental feedbacks

“…The periodic fluctuations of group cooperation and the local environment are shown in Fig 5c and 5d . Such periodic evolution is actually in line with the intuitions from the real world in a way that the group cooperation will neither disappear completely nor always be maintained at the highest level in many complex systems, for instance, the seasonal oscillating dynamics of the COVID-19 infection [ 67 – 70 ], the dynamic adjustment of big companies in the economic cycles and the oscillating abundance of bacteria or cancer cells in periodically varying environments [ 37 , 64 ].…”

“…For instance, companies tend to increase the salary and recruit more employees in bull markets, adopting aggressive expansion strategies as each additional staff could provide much more returns, while on the contrary, they are more likely to cut salaries and reduce the stuff in bear markets. Similarly, changes in nutrient concentration of culture medium or the usage of drugs directly affect the fitness of the competing bacteria or cancer cells [ 37 , 38 , 62 , 64 ]. Such global environmental fluctuations could naturally be reflected and characterized by the nonlinear factor w : a large synergy effect of cooperation corresponds to a good global environment where w > 1, while the discounting of cooperation is related to a bad global environment where w < 1.…”

Optimizing Adaptive Therapy Based on the Reachability to Tumor Resistant Subpopulation

“…In this study, the difference in competition parameters of H1975 and A549 also indicates that the resources used by the two subpopulations are not the same. Therefore, through the administration of osimertinib and the interference of the distinct metabolic pathway of A549, periodic oscillations of subpopulations can be realized in this tumor system [ 28 ], so that system reachability can be maintained for a long time.…”

Clinical Applications of Liquid Biopsy in Prostate Cancer: From Screening to Predictive Biomarker

“…Mathematical models of adaptive treatment strategies have been developed for mCRPC and the feasibility, safety and efficacy of this approach have been investigated in mCRPC with promising results [ 142 , 144 , 145 , 146 , 147 , 148 ]. In a pilot study using a 50%-change in the pretreatment value of PSA as a biomarker to guide initiation or withdrawal of abiraterone, the median time to treatment failure defined as radiographic progression was as long as 27 months with an adaptive strategy, representing a substantial increase compared to 16.5 months with continuous treatment described in the original studies [ 142 , 149 ].…”