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

Area of Science:

• Gynecologic Oncology
• Molecular Pathology
• Precision Medicine

Background:

• Endometrial cancer (EC) is the sole gynecologic malignancy with rising incidence and mortality.
• Standard treatments are effective for early-stage EC, but precision medicine has transformed management.
• Recent genome sequencing identified four distinct EC molecular subtypes.

Purpose of the Study:

• To review current evidence on EC molecular analysis for risk classification and prognostication.
• To guide tailored and targeted therapies for early and advanced/metastatic EC.
• To provide insights into optimal surgical management and future strategies based on molecular classification.

Main Methods:

• Comprehensive literature review of updated evidence on endometrial cancer molecular analysis.
• Analysis of molecular sub-types, risk classification, and prognostication.
• Evaluation of tailored and targeted therapy approaches, including immune-checkpoint inhibitors.

Main Results:

• Molecular analysis enables tailoring of adjuvant treatments, escalating or de-escalating therapy based on specific mutations (e.g., POLE, p53).
• Molecular signatures facilitate the use of novel targeted therapies, notably immune-checkpoint inhibitors, improving prognosis.
• Ongoing research explores further sub-stratifications and treatment options for enhanced precision.

Conclusions:

• Molecular classification is crucial for personalized endometrial cancer management.
• Tailored therapies based on molecular subtypes offer improved oncologic outcomes.
• Continued research into molecular sub-stratifications and novel treatments will further refine EC management.