From genes to clinical practice : exploring the genomic underpinnings of endometrial cancer

Abstract

SIMPLE SUMMARY : Endometrial cancer is becoming more common, and current treatments do not work well for everyone. The study aims to understand how genetic changes drive this type of cancer and how these insights can improve treatment. It explores key genetic mutations and how they influence the development of cancer, with the goal of helping to classify the disease more precisely and design targeted therapies that are tailored to individual patients. By connecting genetics to clinical care, this research could lead to earlier diagnoses, better treatment options, and improved survival rates. It also sets the stage for future studies, giving the scientific community a clearer roadmap to enhance cancer care.

Endometrial cancer (EC), a prevalent gynecological malignancy, presents significant challenges due to its genetic complexity and heterogeneity. The genomic landscape of EC is underpinned by genetic alterations, such as mutations in PTEN, PIK3CA, and ARID1A, and chromosomal abnormalities. The identification of molecular subtypes—POLE ultramutated, microsatellite instability (MSI), copy number low, and copy number high—illustrates the diverse genetic profiles within EC and underscores the need for subtype-specific therapeutic strategies. The integration of multi-omics technologies such as single-cell genomics and spatial transcriptomics has revolutionized our understanding and approach to studying EC and offers a holistic perspective that enhances the ability to identify novel biomarkers and therapeutic targets. The translation of these multi-omics findings into personalized medicine and precision oncology is increasingly feasible in clinical practice. Targeted therapies such as PI3K/AKT/mTOR inhibitors have demonstrated the potential for improved treatment efficacy tailored to specific genetic alterations. Despite these advancements, challenges persist in terms of variability in patient responses, the integration of genomic data into clinical workflows, and ethical considerations. This review explores the genomic underpinnings of EC, from genes to clinical practice. It highlights the ongoing need for multidisciplinary research and collaboration to address the complexities of EC and improve diagnosis, treatment, and patient outcomes.