Radiosensitizers in pancreatic cancer-Preclinical and clinical exploits with molecularly targeted agents

摘要

Radiotherapy (RT) is an integral part of both definitive and palliative cancer management, which is estimated to be indicated in the treatment of 52% of patients with cancer.1 Although RTcan afford local control, the addition of systemic therapy may manage occult distant disease and, in some cases, also offer radiosensitization benefit.2 Yet, the use of conventional cytotoxic chemotherapy as a means of radiosensitization may lead to increased toxicity owing to the lack of specificity for tumor cells. Therefore, there has been evolving interest in identifying agents that selectively target tumor-specific pathways important in RT-induced cell death with the goal of augmenting the effects of RT while minimizing sensitization of normal tissues. Many of the targeted agents, currently studied as potential radiosensitizers, are cytostatic3; although unlike conventional cytotoxic chemotherapies, these agents may avoid or reduce normal tissue toxicity by exploiting molecular differences between malignant and nonmalignant cells.