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Novel targeted therapies in ovarian and uterine carcinosarcomas

Chanhee Han1, Gary Altwerger1, Gulden Menderes1

  • 1Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.

Discovery Medicine
|July 19, 2018
PubMed

Insights

Uterine and ovarian carcinosarcomas (CSs) are aggressive cancers needing new treatments. Genetic studies reveal key mutations in pathways like HER2 and PI3K/AKT/mTOR, offering targets for novel therapies.

Area of Science:

  • Gynecologic Oncology
  • Cancer Genomics
  • Molecular Pathology

Background:

  • Carcinosarcomas (CSs) of the uterus and ovary are rare, aggressive tumors with poor prognoses.
  • Effective treatment strategies for these female genital tract tumors are urgently needed.
  • Recent whole-exome sequencing has identified numerous genetic alterations in CSs.

Purpose of the Study:

  • To review the genetic landscape of uterine and ovarian carcinosarcomas.
  • To explore novel targeted treatment modalities for these rare cancers.

Main Methods:

  • Review of whole-exome sequencing studies.
  • Analysis of identified mutations and aberrant gene/pathway activations.
  • Exploration of targeted therapy implications.

Main Results:

  • CSs exhibit mutations/aberrant activation in multiple genes/pathways, including HER2, PI3K/AKT/mTOR, EGFR, and MAPK.
  • Genes involved in histone and chromatin structure, and cell-cycle regulation are also implicated.
  • The carcinomatous component is hypothesized to drive CS tumorigenesis.

Conclusions:

  • Understanding the genetic landscape of CSs is crucial for developing targeted therapies.
  • Targeted treatment modalities show promise for improving outcomes in patients with these deadly gynecologic tumors.

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