Repopulation of cancer cells during therapy: an important cause of treatment failure

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Abstract
The repopulation of surviving tumour cells during treatment with radiation and chemotherapy is an important cause of treatment failure. The rate of repopulation often increases with time during treatment with either radiotherapy or chemotherapy. Mechanisms that underlie tumour repopulation are poorly understood, but might involve the proliferation of tumour cells that are distant from blood vessels and that were destined to die in the absence of cancer treatment. Prolongation of a course of fractionated radiotherapy requires a substantial increase in total dose, to counter the effects of accelerated repopulation. Accelerated repopulation during successive courses of chemotherapy can lead to an initial response followed by tumour regrowth in the absence of any change in the intrinsic sensitivity of the tumour cells. Accelerated radiotherapy and dose-dense chemotherapy (with support from growth factors) represent promising strategies for reducing the effects of repopulation by shortening the overall treatment time. The use of molecular-targeted cytostatic agents during radiotherapy, or between courses of chemotherapy, is a promising strategy to inhibit repopulation and thereby to improve therapeutic outcome.

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