New therapeutic targets for endometrial cancer: a glimpse into the preclinical sphere

Ilan Bruchim, Ilaria Capasso, Ariel Polonsky, Shilhav Meisel, Vanda Salutari, Haim Werner, Domenica Lorusso, Giovanni Scambia, Francesco Fanfani

Research output: Contribution to journalReview articlepeer-review


Introduction: Endometrial cancer (EC) is the only gynecologic malignancy showing increasing trends in incidence and mortality. While standard treatment has been effective primarily for early-stage EC, precision medicine with tailored therapy has revolutionized the management of this disease. Genome sequencing analyses have identified four sub-types of EC. Treatments for primary and metastatic disease can now be tailored more accurately to achieve better oncologic results. Areas covered: This review provides an overview of the most relevant and updated evidence in the literature regarding EC molecular analysis and its role in risk classification, prognostication, and guidance for tailored and target therapies in early and advanced/metastatic stages. In addition, it provides updated information on optimal surgical management based on molecular classification and highlights key advances and future strategies. Expert opinion: EC molecular analysis yields the potential of tailoring adjuvant treatment by escalating or deescalating therapy, as shown for POLE-mutated and p53-mutated tumors. Moreover, the expression of specific molecular signatures offers the possibility to employ novel target therapies, such as immune-checkpoint inhibitors that have demonstrated a significant benefit on prognosis. New treatment guidelines are still being established, and ongoing studies are exploring the potential prognostic role of further sub-stratifications of the four molecular classes and treatment options.

Original languageEnglish
Pages (from-to)29-43
Number of pages15
JournalExpert Opinion on Therapeutic Targets
Issue number1-2
StatePublished - 12 Feb 2024


  • DNA polymerase epsilon ultra-mutated
  • Endometrial cancer
  • microsatellite unstable hypermutated, p-53-abnormal endometrial cancer
  • mismatch repair deficient endometrial cancer
  • molecular classification
  • Prognosis
  • Humans
  • Endometrial Neoplasms/drug therapy
  • Female
  • Mutation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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