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. Author manuscript; available in PMC: 2023 Jan 1.
Published in final edited form as: Semin Radiat Oncol. 2022 Jan;32(1):54–63. doi: 10.1016/j.semradonc.2021.09.002

Figure 4: Cells tolerate only a limited amount of CIN.

Figure 4:

Cells have evolved multiple mechanisms for accurately maintaining their genomes during mitosis (green zone). Modestly increased rates of CIN (yellow zone), due to defective error correction or weakened mitotic checkpoint signaling, can be tumor promoting due to loss of tumor suppressor genes, for instance. However, further increasing the rate of CIN (into the red zone) results in cell death due to loss of both copies of one or more essential chromosomes. Tumors exhibit variable rates of CIN that fall in either the green or yellow zones prior to treatment. Given that radiation induces CIN, irradiation of tumors in the yellow zone is predicted to increase CIN over a maximally tolerated threshold (dashed line), leading to cell death and tumor regression. However, tumors in the green zone are expected to be more tolerant of radiation induced increases in CIN, since it elevates them into the yellow zone. Increasing CIN above a tolerable threshold in these tumors with a CIN-inducing drug provides a mechanistic opportunity to enhance cancer cell death and radiation response.