Cancer cells utilize the forces of natural selection to evolve evolvability allowing a constant supply of heritable variation that permits a cancer species to evolutionary track changing hazards and opportunities. Over time, the dynamic tumor ecosystem is exposed to extreme, catastrophic changes in the conditions of the tumor—natural (e.g., loss of blood supply) or imposed (therapeutic). While the nature of these catastrophes may be varied or unique, their common property may be to doom the current cancer phenotype unless it evolves rapidly. Poly‐aneuploid cancer cells (PACCs) may serve as efficient sources of heritable variation that allows cancer cells to evolve rapidly, speciate, evolutionarily track their environment, and most critically for patient outcome and survival, permit evolutionary rescue, therapy resistance, and metastasis. As a conditional evolutionary strategy, they permit the cancer cells to accelerate evolution under stress and slow down the generation of heritable variation when conditions are more favorable or when the cancer cells are closer to an evolutionary optimum. We hypothesize that they play a critical and outsized role in lethality by their increased capacity for invasion and motility, for enduring novel and stressful environments, and for generating heritable variation that can be dispensed to their 2N+ aneuploid progeny that make up the bulk of cancer cells within a tumor, providing population rescue in response to therapeutic stress. Targeting PACCs is essential to cancer therapy and patient cure—without the eradication of the resilient PACCs, cancer will recur in treated patients.

中文翻译：

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多非整倍体癌细胞促进进化，产生致命的癌症。


癌细胞利用自然选择的力量来进化，从而不断提供可遗传的变异，从而使癌症物种能够进化跟踪不断变化的危险和机会。随着时间的推移，动态的肿瘤生态系统会面临肿瘤状况的极端、灾难性的变化——自然的（例如，血液供应丧失）或强加的（治疗性的）。虽然这些灾难的性质可能各不相同或独特，但它们的共同特性可能是毁灭当前的癌症表型，除非它迅速发展。多非整倍体癌细胞（PACC）可以作为可遗传变异的有效来源，使癌细胞能够快速进化、形成物种、进化跟踪其环境，并且对于患者的结果和生存最关键的是，允许进化拯救、治疗抵抗和转移。作为一种条件进化策略，它们允许癌细胞在压力下加速进化，并在条件更有利或癌细胞更接近进化最佳时减缓可遗传变异的产生。我们假设它们在致死率方面发挥着关键而巨大的作用，因为它们具有增强的侵袭和运动能力、忍受新的和有压力的环境的能力，以及产生可遗传变异的能力，这些变异可以分配给构成癌细胞大部分的2N+非整倍体后代。在肿瘤内，为应对治疗压力提供群体救援。以 PACC 为靶点对于癌症治疗和患者治愈至关重要——如果不根除有弹性的 PACC，癌症就会在接受治疗的患者中复发。