Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

Int J Mol Sci. 2017 May 20;18(5):1100. doi: 10.3390/ijms18051100.

Abstract

Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2-5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50-80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms "uterine carcinosarcoma", "uterine Malignant Mixed Müllerian Tumors", "target therapies", "angiogenesis therapy", "cancer stem cell therapy", "prognostic biomarker", and "novel antibody-drug". Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

Keywords: carcinosarcomas; epigenetics; genetics; immunotherapy; uterine cancer.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Bispecific / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinosarcoma / drug therapy*
  • Carcinosarcoma / pathology
  • Epigenesis, Genetic
  • Epithelial Cell Adhesion Molecule / antagonists & inhibitors
  • Epithelial Cell Adhesion Molecule / genetics
  • Epithelial Cell Adhesion Molecule / metabolism
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunotherapy
  • Mixed Tumor, Mullerian / drug therapy*
  • Mixed Tumor, Mullerian / pathology
  • Molecular Targeted Therapy / methods*
  • Neovascularization, Pathologic
  • Prognosis
  • Survival Rate
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / pathology

Substances

  • Antibodies, Bispecific
  • Biomarkers, Tumor
  • Epithelial Cell Adhesion Molecule
  • ErbB Receptors
  • catumaxomab