title: Molecularly targeted agents as radiosensitizers in cancer therapy--focus on prostate cancer.
abstract: As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Alcorn
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Walker
authors.forename: Nishant
authors.initials: N
authors.lastname: Gandhi
authors.forename: Amol
authors.initials: A
authors.lastname: Narang
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wild
authors.forename: Russell K
authors.initials: RK
authors.lastname: Hales
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Danny Y
authors.initials: DY
authors.lastname: Song
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Deweese
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
authors.forename: Phuoc T
authors.initials: PT
authors.lastname: Tran
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018841:HSP90 Heat-Shock Proteins; D011838:Radiation-Sensitizing Agents; D066246:ErbB Receptors; D019061:src-Family Kinases; D058570:TOR Serine-Threonine Kinases