Artzy-Randrup Yael, Epstein Tamir, Brown Joel S, Costa Ricardo L B, Czerniecki Brian J, Gatenby Robert A
Department of Theoretical and Computational Ecology, IBED, University of Amsterdam, Amsterdam, The Netherlands.
Institute of Advanced Study, University of Amsterdam, Amsterdam, The Netherlands.
NPJ Breast Cancer. 2021 Mar 11;7(1):26. doi: 10.1038/s41523-021-00230-y.
Disseminated cancer cells (DCCs) are detected in the circulation and bone marrow of up to 40% of breast cancer (BC) patients with clinically localized disease. The formation of metastases is governed by eco-evolutionary interactions of DCCs with the tissue during the transition from microscopic populations to macroscopic disease. Here, we view BC adjuvant and neoadjuvant treatments in the context of small population extinction dynamics observed in the Anthropocene era. Specifically, the unique eco-evolutionary dynamics of small asexually reproducing cancer populations render them highly vulnerable to: (1) environmental and demographic fluctuations, (2) Allee effects, (3) genetic drift and (4) population fragmentation. Furthermore, these typically interact, producing self-reinforcing, destructive dynamics-termed the Extinction Vortex-eradicating the population even when none of the perturbations is individually capable of causing extinction. We propose that developing BC adjuvant and neoadjuvant protocols may exploit these dynamics to prevent recovery and proliferation of small cancer populations during and after treatment-termed "Eco-evolutionary rescue" in natural extinctions. We hypothesize more strategic application of currently available agents based on the extinction vulnerabilities of small populations could improve clinical outcomes.
在高达40%的临床局限性乳腺癌（BC）患者的循环系统和骨髓中可检测到播散癌细胞（DCCs）。从微小细胞群向宏观疾病转变过程中，转移灶的形成受DCCs与组织间生态进化相互作用的支配。在此，我们从人类世时代观察到的小种群灭绝动态角度审视BC辅助治疗和新辅助治疗。具体而言，小型无性繁殖癌种群独特的生态进化动态使其极易受到以下因素影响：（1）环境和人口波动；（2）阿利效应；（3）遗传漂变；（4）种群碎片化。此外，这些因素通常相互作用，产生自我强化的破坏性动态——即所谓的“灭绝漩涡”——即使没有任何一个干扰因素单独能够导致灭绝，也会使种群灭绝。我们提出，制定BC辅助治疗和新辅助治疗方案可利用这些动态来防止治疗期间及之后小癌种群的恢复和增殖——这在自然灭绝中被称为“生态进化拯救”。我们假设，基于小种群的灭绝脆弱性，更具策略性地应用现有药物可能会改善临床结果。
