Dataset Information

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.

SUBMITTER: Soberanis Pina P

PROVIDER: S-EPMC10962462 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Soberanis Pina Pamela P Lheureux Stephanie S

Biologics : targets & therapy 20240321

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 person ...[more]

PMID: 38529411

Similar Datasets

Project description:Endometrial cancer is primarily treated with surgery. Adjuvant treatment strategies for endometrial cancer, such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined chemotherapy and radiotherapy, have been studied in several randomized trials. Adjuvant treatment is currently based on the presence of clinico-pathological risk factors. Low-risk disease is adequately managed with surgery alone. In high-intermediate risk endometrial cancer, adjuvant vaginal brachytherapy is recommended to maximize local control, with only mild side effects and without impact on quality of life. For high-risk endometrial cancer, recent large randomized trials support the use of pelvic radiotherapy, especially in stage I-II endometrial cancer with risk factors. For women with serous cancers and those with stage III disease, chemoradiation increased both recurrence-free and overall survival, while GOG-258 showed similar recurrence-free survival compared with six cycles of chemotherapy alone, but with better pelvic and para-aortic nodal control with combined chemotherapy and radiotherapy. Recent molecular studies, most notably the work from The Cancer Genome Atlas (TCGA) project, have shown that four endometrial cancer molecular classes can be distinguished; POLE ultra-mutated, microsatellite instable hypermutated, copy-number-low, and copy-number-high. Subsequent studies, using surrogate markers to identify groups analogous to TCGA sub-classes, showed that all four endometrial cancer sub-types are found across all stages, histological types, and grades. Moreover, the molecular sub-groups have proved to have a stronger prognostic impact than histo-pathological tumor characteristics. This introduces an new era of molecular classification based diagnostics and treatment approaches. Integration of the molecular factors and new therapeutic targets will lead to molecular-integrated adjuvant treatment including targeted treatments, which are the rationale of new and ongoing trials. This review presents an overview of current adjuvant treatment strategies in endometrial cancer, highlights the development and evaluation of a molecular-integrated risk profile, and briefly discusses ongoing developments in targeted treatment.

Project description:BACKGROUND: The number of patients with endometrial carcinoma (EmCa) with advanced stage or high histological grade is increasing and prognosis has not improved for over the last decade. There is an urgent need for the discovery of novel molecular targets for diagnosis, prognosis and treatment of EmCa, which will have the potential to improve the clinical strategy and outcome of this disease. METHODOLOGY AND RESULTS: We used a "drill-down" proteomics approach to facilitate the identification of novel molecular targets for diagnosis, prognosis and/or therapeutic intervention for EmCa. Based on peptide ions identified and their retention times in the first LC-MS/MS analysis, an exclusion list was generated for subsequent iterations. A total of 1529 proteins have been identified below the Proteinpilot® 5% error threshold from the seven sets of iTRAQ experiments performed. On average, the second iteration added 78% new peptides to those identified after the first run, while the third iteration added 36% additional peptides. Of the 1529 proteins identified, only 40 satisfied our criteria for significant differential expression in EmCa in comparison to normal proliferative tissues. These proteins included metabolic enzymes (pyruvate kinase M2 and lactate dehydrogenase A); calcium binding proteins (S100A6, calcyphosine and calumenin), and proteins involved in regulating inflammation, proliferation and invasion (annexin A1, interleukin enhancer-binding factor 3, alpha-1-antitrypsin, macrophage capping protein and cathepsin B). Network analyses revealed regulation of these molecular targets by c-myc, Her2/neu and TNF alpha, suggesting intervention with these pathways may be a promising strategy for the development of novel molecular targeted therapies for EmCa. CONCLUSIONS: Our analyses revealed the significance of drill-down proteomics approach in combination with iTRAQ to overcome some of the limitations of current proteomics strategies. This study led to the identification of a number of novel molecular targets having therapeutic potential for targeted molecular therapies for endometrial carcinoma.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets