title: Successful control of heavily pretreated metastatic gastric cancer with the mTOR inhibitor everolimus (RAD001) in a patient with PIK3CA mutation and pS6 overexpression.
abstract: BACKGROUND
  Everolimus (RAD001) is an orally administered mTOR inhibitor that is well known for its antitumor efficacy and that has been approved for the treatment of several solid tumors, including renal cell carcinoma. In gastric cancer (GC), despite previous preclinical and phase I/II studies suggesting the promising efficacy of everolimus in previously treated AGC, more recent trials revealed that only certain subsets of patients might benefit from treatment with everolimus.
  
  
  METHODS
  A 26-year-old man with metastatic gastric cancer with multiple liver lesions was treated with everolimus after failure of 1st-line and 2nd-line chemotherapy. A durable partial response was achieved for over 2 years. After progression from initial everolimus treatment, sequential cytotoxic chemotherapies were tried but failed rapidly. Everolimus was re-tried as salvage chemotherapy (re-treatment), and the patient achieved stable disease for 1 year until his death. Subsequent mutational analysis and immunohistochemical (IHC) staining with the tumor tissues just before re-treatment with everolimus revealed a PIK3CA hotspot mutation and pS6 overexpression in the primary tumor. After two cycles of everolimus re-treatment, the overexpression of pS6 became nearly absent in follow-up IHC staining.
  
  
  CONCLUSIONS
  Everolimus monotherapy was satisfactory in a patient with refractory metastatic GC harboring PIK3CA and pS6 aberrations. These molecular alterations might be potential biomarkers that can predict the treatment response of everolimus, particularly in the terms of durable disease control. This case suggests and emphasizes that close evaluation of biomarkers in tumor tissue may be essential for identifying highly favorable groups among various subpopulations with AGC.
authors.affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. irvineusa@hanmail.net.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. minuryu@amc.seoul.kr.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. ysoopark@amc.seoul.kr.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. srpark@amc.seoul.kr.
authors.forename: Sook Ryun
authors.initials: SR
authors.lastname: Park
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. youngsoon@amc.seoul.kr.
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Na
authors.affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. ryooby@amc.seoul.kr.
authors.forename: Baek-Yeol
authors.initials: BY
authors.lastname: Rhoo
authors.affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. ykkang@amc.seoul.kr.
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058534:Class I Phosphatidylinositol 3-Kinases; D000068338:Everolimus / Q000494:pharmacology / Q000627:therapeutic use*; D017809:Fatal Outcome; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D058534:Class I Phosphatidylinositol 3-Kinases; D000068338:Everolimus; D019869:Phosphatidylinositol 3-Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C484760:PIK3CA protein, human