Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

Abstract

Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy.

Keywords: DNA damage repair; GH-IGF1 signaling pathway; cancers; radio-resistance; radiotherapy.