Biomarkers and immunotherapy in endometrial cancer: mechanisms and clinical applications

Area of Science:

• Gynecologic Oncology
• Immunotherapy
• Molecular Pathology

Background:

• Advanced endometrial cancer (EC) presents significant treatment challenges due to its complex molecular landscape and ability to evade immune responses.
• Immune checkpoint inhibitors (ICIs) offer therapeutic potential, particularly for subtypes like mismatch repair-deficient (MMRd) and POLE-mutated EC, yet treatment resistance is a major hurdle.

Purpose of the Study:

• To review recent advancements in biomarker-driven immunotherapy for advanced endometrial cancer.
• To explore predictive biomarkers, combination strategies, and challenges in the clinical application of immunotherapy for EC.

Main Methods:

• Literature review synthesizing current research on EC immunotherapy.
• Analysis of predictive biomarkers including LRP2, FANCE, MSH2, and miRNA signatures.
• Examination of combination therapies (e.g., ICIs with anti-angiogenics, PARP inhibitors) and their impact on the tumor microenvironment.

Main Results:

• Biomarkers like LRP2, FANCE, MSH2, and miRNA signatures are emerging as predictors of response to immunotherapy in EC.
• Combination strategies involving ICIs show potential for overcoming resistance, with anti-angiogenics and PARP inhibitors being key agents.
• Tumor microenvironment factors significantly influence immunotherapy efficacy, necessitating a deeper understanding for personalized treatment approaches.

Conclusions:

• Biomarker-driven immunotherapy holds significant promise for treating advanced endometrial cancer, particularly in specific molecular subtypes.
• Overcoming resistance through combination therapies and leveraging emerging technologies like machine learning are crucial for advancing personalized immunotherapy in EC.
• Standardization of biomarker testing and optimized clinical trial designs are essential for translating these advances into improved patient outcomes.