We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this theory is the formation of simultaneously polyploid and aneuploid cancer cells, polyaneuploid cancer cells (PACCs), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest. The theory is independent of which of the classically associated oncogenic mutations have already occurred. PACCs have been generally disregarded as senescent or dying cells. Our theory states that therapeutic resistance is driven by PACC formation that is enabled by accessing a polyploid program that allows an aneuploid cancer cell to double its genomic content, followed by entry into a nondividing cell state to protect DNA integrity and ensure cell survival. Upon removal of stress, e.g., chemotherapy, PACCs undergo depolyploidization and generate resistant progeny that make up the bulk of cancer cells within a tumor.

我们提出了一个统一的理论来解释癌症的复发，治疗耐药性和致死性。该理论的基础是同时形成多倍体和非整倍体癌细胞，即多非整倍体癌细胞（PACC），它们通过进入细胞周期停滞状态而避免了全身疗法的毒性作用。该理论与已经发生的经典关联的致癌突变无关。通常将PACC视为衰老或垂死细胞。我们的理论认为，治疗耐药性是由PACC形成驱动的，该过程可通过访问一个多倍体程序来实现，该程序使非整倍性癌细胞的基因组含量翻倍，然后进入非分裂细胞状态以保护DNA完整性并确保细胞存活。消除压力（例如化疗）后，