title: Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer.
abstract: OBJECTIVE
  This review highlights selective androgen receptor modulators (SARMs) as emerging agents in late-stage clinical development for the prevention and treatment of muscle wasting associated with cancer.
  
  
  RESULTS
  Muscle wasting, including a loss of skeletal muscle, is a cancer-related symptom that begins early in the progression of cancer and affects a patient's quality of life, ability to tolerate chemotherapy, and survival. SARMs increase muscle mass and improve physical function in healthy and diseased individuals, and potentially may provide a new therapy for muscle wasting and cancer cachexia. SARMs modulate the same anabolic pathways targeted with classical steroidal androgens, but within the dose range in which expected effects on muscle mass and function are seen androgenic side-effects on prostate, skin, and hair have not been observed. Unlike testosterone, SARMs are orally active, nonaromatizable, nonvirilizing, and tissue-selective anabolic agents.
  
  
  CONCLUSIONS
  Recent clinical efficacy data for LGD-4033, MK-0773, MK-3984, and enobosarm (GTx-024, ostarine, and S-22) are reviewed. Enobosarm, a nonsteroidal SARM, is the most well characterized clinically, and has consistently demonstrated increases in lean body mass and better physical function across several populations along with a lower hazard ratio for survival in cancer patients. Completed in May 2013, results for the Phase III clinical trials entitled Prevention and treatment Of muscle Wasting in patiEnts with Cancer1 (POWER1) and POWER2 evaluating enobosarm for the prevention and treatment of muscle wasting in patients with nonsmall cell lung cancer will be available soon, and will potentially establish a SARM, enobosarm, as the first drug for the prevention and treatment of muscle wasting in cancer patients.
authors.affiliation: All authors work for GTx, Inc., Memphis, Tennessee, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Dalton
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Taylor
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mohler
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Steiner
mesh_terms: D045930:Anabolic Agents / Q000627:therapeutic use; D000726:Androgen Antagonists / Q000627:therapeutic use*; D059002:Androgen Receptor Antagonists; D002100:Cachexia / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D045930:Anabolic Agents; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen