Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

Simple Summary Endometrial cancer is a complex disease with multiple risk factors, distinct histological subtypes, and a variety of available therapeutic options. The disease's pathogenesis involves several molecular mechanisms, such as genetic mutations, defects in the DNA mismatch repair (MMR) pathway, hormonal signaling pathway imbalances, epigenetic changes, and disturbances in angiogenesis. On the other hand, molecular biomarkers seem to have an essential role in the diagnosis, prognosis, prediction of therapeutic response, and monitoring of disease progression in endometrial cancer. This review highlights the most significant dysregulated molecular mechanisms and reveals the relationship between specific biomarkers and targeted therapy approaches in the fight against endometrial cancer.Abstract Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient's life.