Basis of cell kill following clinical radiotherapy

Over one half of cancer patients are treated radiotherapy. Technological advances in radiation targeting and concurrent chemotherapy continue to improve clinical radiotherapy outcome. Modem radiotherapy clinical trials are ongoing with novel molecular-targeted agents, requiring an increased understanding of cell death signals in a tissue-specific manner. Herein, we critically appraise the relative roles of apoptosis, mitotic catastrophe and terminal growth arrest in relation to final clonogenic cell kill following radiotherapy. Mitotic catastrophe and terminal growth arrest form the basis of the majority of cell kill during radiotherapy for common epithelial tumors (e.g. prostate, breast, lung, etc.) whereas more sensitive tumors (e.g. lymphomas or germ cell tumors) undergo apoptosis. Targeting of apoptotic, cell cycle checkpoint and DNA repair pathways may further augment cell kill from all three death pathways. Using intra-treatment biopsies or non-invasive imaging may soon allow for prediction of individual patient response and judicial selection of molecular targeting based on specific tumor cell signaling.