Journal Article

Strategies for optimizing the response of cancer and normal tissues to radiation

Moding, Everett J., Kastan, Michael B., Kirsch, David G.

2013

Overview

Key Points More than half of all patients with cancer receive radiation therapy. Normal tissue tolerance for radiation limits the dose of radiation that can safely be delivered, which can limit the probability of curing a tumour. As our knowledge of the mechanisms and signalling pathways that determine the response of tumour tissues and normal tissues to radiation increases, targeted drugs can be developed that selectively sensitize tumours or protect normal tissues. Promising approaches to selectively enhance tumour radiosensitivity include triggering synthetic lethality, inhibiting multiple targets to simultaneously block more than one signalling pathway and targeting the tumour microenvironment. More than half of all patients with cancer receive radiation therapy, but normal tissue tolerance to radiation often limits the ability to cure tumours with radiation therapy. Here, Moding, Kastan and Kirsch discuss current approaches and possible future directions for combining radiation therapy with targeted therapies to enhance the probability of tumour cure. Approximately 50% of all patients with cancer receive radiation therapy at some point during the course of their treatment, and the majority of these patients are treated with curative intent. Despite recent advances in the planning of radiation treatment and the delivery of image-guided radiation therapy, acute toxicity and potential long-term side effects often limit the ability to deliver a sufficient dose of radiation to control tumours locally. In the past two decades, a better understanding of the hallmarks of cancer and the discovery of specific signalling pathways by which cells respond to radiation have provided new opportunities to design molecularly targeted therapies to increase the therapeutic window of radiation therapy. Here, we review efforts to develop approaches that could improve outcomes with radiation therapy by increasing the probability of tumour cure or by decreasing normal tissue toxicity.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67 / 692/699/67/1059/485 / Acute toxicity / Analysis / Animals / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - therapeutic use / Biomedicine / Biotechnology / Cancer / Cancer Research / Care and treatment / Chemoradiotherapy - adverse effects / Chemoradiotherapy - methods / Dose-Response Relationship, Radiation / Health aspects / Humans / Medicinal Chemistry / Molecular Medicine / Neoplasms - metabolism / Neoplasms - pathology / Neoplasms - radiotherapy / Nuclear radiation / Pharmacology/Toxicology / Radiation Dosage / Radiation-Protective Agents - therapeutic use / Radiation-Sensitizing Agents - administration & dosage / Radiation-Sensitizing Agents - therapeutic use / Radiotherapy / Radiotherapy, Image-Guided - adverse effects / Radiotherapy, Image-Guided - methods / Radiotherapy, Intensity-Modulated - adverse effects / Radiotherapy, Intensity-Modulated - methods / review-article