title: Successful use of next generation genomic sequencing (NGS)-directed therapy of clear cell carcinoma of the ovary (CCCO) with trametinib and metformin in a patient with chemotherapy-refractory disease.
abstract: OBJECTIVE
  Compared to other subtypes of epithelial ovarian cancer, clear cell carcinoma of the ovary bears an ominous reputation for chemotherapy resistance, increased relapse rate, and diminished survival. Among patients with distinct histopathologic subtypes, molecular analyses have identified a variety of known drivers of the malignant behavior, and depict a striking heterogeneity.
  
  
  METHODS
  A patient with rapidly metastatic CCCO that was refractory to taxane, platinum, pemetrexed, and bevacizumab-based strategies underwent molecular profiling which disclosed dual MAPK and PI3K/AKT/mTOR pathway mutations.
  
  
  RESULTS
  Combined targeted therapy with trametinib and metformin resulted in a dramatic disease regression without toxicity.
  
  
  CONCLUSIONS
  The case highlights the utility of precision medicine combining individual molecular diagnosis with rational therapeutic intervention with targeted agents.
authors.affiliation: Personalized Cancer Medicine PLLC, 1329 Lusitana St. Suite 609, Honolulu, HI 96813 USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Castro
authors.affiliation: Division of Gynecologic Oncology, Tripler Army Medical Center, TAMC, Honolulu, HI USA.
authors.forename: Bradford P
authors.initials: BP
authors.lastname: Whitcomb
authors.affiliation: The Clearity Foundation, 4365 Executive Drive Suite 1500, San Diego, CA 92121 USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Zajchowski
authors.affiliation: Department of Gynecologic Oncology & Reproductive Medicine, Clinical Research Programs, University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Dr., CPB 6.3590, Houston, TX 77030 USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
keywords: Clear cell carcinoma; Genomic; KRAS mutation; Metformin; Molecular profiling; Next generation sequencing; Ovarian cancer; PIK3CA mutation; Personalized medicine; Precision medicine; Targeted therapy; Trametinib