Low-grade serous carcinoma: new concepts and emerging therapies

Gynecol Oncol. 2013 Sep;130(3):660-6. doi: 10.1016/j.ygyno.2013.05.021. Epub 2013 May 23.

Abstract

For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance leading to separate clinical trials for patients with this subtype originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20-40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare - about 5%. Primary treatment of low-grade serous carcinoma includes surgery+platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormonal therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations.

Keywords: Low-grade serous; MAP kinase; MEK inhibitor; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Female
  • Gene Expression
  • Humans
  • Neoplasm Grading
  • Neoplasms, Glandular and Epithelial / embryology
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology*
  • Neoplasms, Glandular and Epithelial / therapy
  • Ovarian Neoplasms / embryology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy