Enhancement of radiotherapy with DNA topoisomerase I-targeted drugs.
Since its discovery more than a century ago, ionizing radiation has become a mainstay therapy for patients suffering from cancers. Currently, radiotherapy provides cure or palliative care for approximately one half of the cancer population. The anticancer efficacy of radiotherapy is, however, largely limited by its lack of tumor specificity and, consequently, normal tissue toxicity. There is an urgent need to develop systemic adjuncts that can enhance the efficacy and the selectivity of radiotherapy toward tumor cells. DNA topoisomerase I (TOP1)-targeted drugs such as camptothecin derivatives represent a novel class of chemotherapeutic agents that have recently been shown to be excellent radiation sensitizers. Combined modality therapy with TOP1-targeted drugs and radiotherapy represents a new promising cancer therapy. The mechanism of enhancement of radiotherapy by TOP1-targeted drugs is under intense investigation. Clinical trials using combinations of radiation and camptothecin derivatives are also currently ongoing in various solid tumors including brain, head and neck, and lung cancers. A better understanding of the radiosensitization (RS) mechanism of TOP1-targeted drugs is pivotal to their clinical application, as well as in guiding the development of better radiation sensitizers.
Chen
Allan Y
AY
Department of Radiation Oncology, UC Davis Medical Center, 4501 X Street, Suite G-126, Sacramento, CA 95817, USA. aychen@ucdavis.edu
Chou
Rachel
R
Shih
Shyh-Jen
SJ
Lau
Derick
D
Gandara
David
D
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin