Molecular Pathways: Targeting Cancer Stem Cells Awakened by Chemotherapy to Abrogate Tumor Repopulation

Cytotoxic chemotherapy remains the first-line therapy for many advanced solid tumors; hence, understanding the underlying mechanisms to overcome chemoresistance remains a top research priority. In the clinic, chemotherapy is administered in multiple cycles that are spaced out to allow the recovery or repopulation of normal tissues and tissue stem cells between treatment cycles. However, residual surviving cancer cells and cancer stem cells can also repopulate tumors during the gap periods between chemotherapy cycles. Tumor repopulation is a phenomenon that has not been well studied; it is often overlooked due to current customized experimental study strategies. Recent findings reveal an alarming role for dying cells targeted by chemotherapy in releasing mitogens to stimulate active repopulation of quiescent cancer stem cells. Therefore, new therapeutic options to abrogate tumor repopulation will provide new avenues to improve chemotherapeutic response and clinical outcome.