Nondiploid cancer cells: Stress, tolerance and therapeutic inspirations

Aberrant ploidy status is a prominent characteristic in malignant neoplasms. Approximately 90% of solid tumors and 75% of haematopoietic malignancies contain aneuploidy cells, and 30%-60% of tumors undergo whole-genome doubling, indicating that nondiploidy might be a prevalent genomic aberration in cancer. Although the role of aneuploid and polyploid cells in cancer remains to be elucidated, recent studies have suggested that nondiploid cells might be a dangerous minority that severely challenges cancer management. Ploidy shifts cause multiple fitness coasts for cancer cells, mainly including genomic, proteotoxic, metabolic and immune stresses. However, nondiploid comprises a well-adopted subpopulation, with many tolerance mechanisms evident in cells along with ploidy shifts. Aneuploid and polyploid cells elegantly maintain an autonomous balance between the stress and tolerance during adaptive evolution in cancer. Breaking the balance might provide some inspiration for ploidy-selective cancer therapy and alleviation of ploidy-related chemoresistance. To understand of the complex role and therapeutic potential of nondiploid cells better, we reviewed the survival stresses and adaptive tolerances within nondiploid cancer cells and summarized therapeutic ploidy-selective alterations for potential use in developing future cancer therapy.