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. Author manuscript; available in PMC: 2023 Sep 1.
Published in final edited form as: Nat Rev Endocrinol. 2022 Nov 29;19(3):134–150. doi: 10.1038/s41574-022-00773-5

Fig 1. Challenges in tumor initiation.

Fig 1.

Cells must surmount multiple hurdles to form a tumor. While the primary cell responsible for initiating a tumor can vary between and even within tumor types, the cancer cell of origin is often a stem/progenitor cell or a cell that has acquired the ability to re-enter the cell cycle and undergo aberrant proliferation. To form a tumor, these cancer-initiating cells must evade differentiation and senescence to undergo successive population doublings. Cancer cells must also resist challenges such as immune recognition or cell death induced by changes in tissue architecture or local metabolism. Within an established tumor, a sub-population of “tumor-initiating cells” with stem-like features have the potential to re-initiate tumors; these cells are often therapy-resistant and responsible for cancer relapse after treatment.