Novel Molecular Targets in Endometrial Cancer: Mechanisms and Perspectives for Therapy

Abstract

Endometrial cancer (EC) has a high epidemiological impact with incidence and mortality rising worldwide. In recent years, the integration of the pathologic and molecular classification has provided relevant information to understand the heterogeneity in the biology of EC, which led to the evolution in the management of patients. Currently, therapeutic breakthroughs have been made in advanced EC to improve oncologic outcomes, with efforts to include patient reported outcomes. Precision and personalized medicine are under way in EC exploring different combination approaches to target cross-talk pathways, cancer cell microenvironment, and metabolic vulnerabilities and improve drug delivery. Yet, collaborative efforts are needed to face the challenges in practice by refining patient selection, ideal biomarker identification, and de-escalation of therapies according to emerging molecular and genomic features of EC.

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

“…These approaches aim to improve the antitumor immune response, overcome immunotherapy resistance, and enhance treatment outcomes for patients with advanced or recurrent EC. Ongoing research and clinical trials are crucial to improve outcomes and patient care in EC by optimizing the selection of appropriate combination therapies, identifying predictive biomarkers, and developing personalized treatment strategies (Table 1) [174]. Immunotherapy + Radiotherapy Pembrolizumab after radiotherapy [175] Immunotherapy + Chemotherapy Pembrolizumab + Doxorubicin [176] Pembrolizumab + Paclitaxel + Carboplatin [177] Radiotherapy + Chemotherapy + Immunotherapy Radiotherapy + Carboplatin or Paclitaxel + Bevacizumab [138,178] Immunotherapy + Anti-angiogenic therapy Pembrolizumab + Lenvatinib [179,180] Chemotherapy + Immunotherapy + Anti-angiogenic therapy Cisplatin + Pembrolizumab + Lenvatinib [152] Immunotherapy + PAPP inhibitors Olaparib + Durvalumab [181,182] Anti-Her2 Therapy + Chemotherapy Trastuzumab + Carboplatin + Paclitaxel [183] With increased clinical experience and supported by advanced scientific research, tumor immunotherapy can be better understood, leading to an innovative and safe approach to treating cancer patients.…”

“…These approaches aim to improve the antitumor immune response, overcome immunotherapy resistance, and enhance treatment outcomes for patients with advanced or recurrent EC. Ongoing research and clinical trials are crucial to improve outcomes and patient care in EC by optimizing the selection of appropriate combination therapies, identifying predictive biomarkers, and developing personalized treatment strategies ( Table 1 ) [ 174 ].…”

Insights into MLH1 Methylation in Endometrial Adenocarcinoma through Pyrosequencing Analysis: A Retrospective Observational Study

“…This molecular subtype is typically lower-grade with positive estrogen and progesterone receptors, making it generally sensitive to hormonal therapy due to its association with estrogen exposure. In contrast, the high copy number subtype is characterized by high genomic instability and frequent TP53 mutations, leading to a worse prognosis and a poorer response to standard therapies [ 11 , 12 , 13 , 14 ].…”