title: Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data.
abstract: BACKGROUND
  mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers.
  
  
  METHODS
  A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results.
  
  
  RESULTS
  A total of 23 studies including 980 patients were considered eligible for our review. Our review included 16 phase II and 7 phase I studies with the majority of patients having uterine cancers. Regarding Endometrial cancer, the CBR ranged from 21% to 60% and median PFS from 2.8 months to 7.3 months. In Ovarian cancers, CBR ranged from 24% to 50% and median PFS from 3.2 months to 5.9 months. In the single phase II study in cervical cancer the CBR was 61% and median PFS was 3.5 months. The toxicity profile was consistent with what was observed previously in other malignancies with fatigue, mucositis, and hematological toxicities being the most common adverse events observed.
  
  
  CONCLUSIONS
  mTOR inhibitors seem to be a promising option in the second line management of advanced gynecological cancers with best safety and efficacy outcomes when given as a single agent or in combination with hormonal treatment. More research is needed for better patient selection.
authors.affiliation: Clinical Oncology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address: loay.kassem@cairocure.com.
authors.forename: Loay
authors.initials: L
authors.lastname: Kassem
authors.affiliation: Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
mesh_terms: D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Cervical cancer; Endometrial cancer; Everolimus; Ovarian cancer; Temsirolimus