Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer

Discov Med. 2016 Apr;21(116):293-303.

Abstract

Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer. Although it represents only 10% of all endometrial cancer cases, USC accounts for up to 40% of all endometrial cancer-related recurrences and subsequent deaths. With such a dismal prognosis, there is an expanding role for novel targeted approaches in the treatment of USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. The results emphasize the relevance of these novel therapeutic targets for biologic therapy of USC, which will be reviewed in this article.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Cyclin E / antagonists & inhibitors
  • Cyclin E / genetics
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology
  • Cystadenocarcinoma, Serous / therapy*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / therapy*
  • Epothilones / therapeutic use
  • Exome / genetics
  • Female
  • Humans
  • Molecular Targeted Therapy / methods*
  • Mutation
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Phosphatase 2 / genetics
  • Radioimmunotherapy
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Sequence Analysis, DNA
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics
  • Tubulin Modulators / therapeutic use
  • Tumor Suppressor Protein p53 / genetics
  • Uterine Neoplasms / genetics
  • Uterine Neoplasms / mortality
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / therapy*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CCNE1 protein, human
  • Cyclin E
  • Epothilones
  • Oncogene Proteins
  • PPP2R1A protein, human
  • Protein Kinase Inhibitors
  • TP53 protein, human
  • Tubulin Modulators
  • Tumor Suppressor Protein p53
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • TOR Serine-Threonine Kinases
  • Protein Phosphatase 2