Fig. 2.

Responses of cancer cells to radiotherapy and chemotherapy. A completely sensitive response is ideal but rare, while radiotherapy and chemotherapy are usually impeded by acquired or intrinsic resistance. Acquired resistance can be loosely divided into cancer stem cell (CSC)-mediated and non-CSC-mediated resistance. CSC-mediated resistance is attributed to the potential ability of CSCs to proliferate and differentiate, which results in regressed tumor recurrence or seeds new tumors in a new place via metastasis. Non-CSC-mediated resistance factors include therapy stress-induced secondary mutations, tumor heterogeneity, altered endoplasmic reticulum (ER) stress, autophagy, drug distribution and metabolism, and so on. The intrinsic resistance mechanisms are similar to those mediating acquired resistance, but the difference is that the characteristics in intrinsic resistance are inherent and not induced by therapy stress