Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer.

Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells' survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms.

The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers.

BRCA1 and BRCA2 germline alterations highly predispose women to breast and ovarian cancers. They are mostly found within the TNBC (Triple-Negative Breast Cancer) and the HGSOC (High-Grade Serous Ovarian Carcinoma) subsets, known by an aggressive phenotype, the lack of therapeutic targets and poor prognosis. Importantly, there is an increased risk for cervical cancer in BRCA1 and BRCA2 mutation carriers that raises questions about the link between the HPV-driven genome instability and BRCA1 and BRCA2 germline mutations. Clinical, preclinical, and in vitro studies explained the increased risk for breast and ovarian cancers by genome instability resulting from the lack or loss of many functions related to BRCA1 or BRCA2 proteins such as DNA damage repair, stalled forks and R-loops resolution, transcription regulation, cell cycle control, and oxidative stress. In this review, we decipher the relationship between BRCA1/2 alterations and genomic instability leading to gynecomammary cancers through results from patients, mice, and cell lines. Understanding the early events of BRCA1/2-driven genomic instability in gynecomammary cancers would help to find new biomarkers for early diagnosis, improve the sensitivity of emerging therapies such as PARP inhibitors, and reveal new potential therapeutic targets.