ONCOBEGLUT

Breast cancer, which accounts for more than 3% of deaths among women in Spain, is the most common type of cancersubject worldwide. Despite clinical advances in recent years, greater efforts are needed in the search for new therapeutic targets and potential treatments. Furthermore, obesity is associated with a wide range of comorbidities, including an increased risk of breast cancer in postmenopausal women, as well as lower survival rates. Among the causes of the association between obesity and breast cancer, increased estrogen levels, dysregulation of carbohydrate metabolism, and chronic low- Degree e inflammation have been described, all of which promote tumor development . Peripheral insulin resistance, common in people with obesity, can lead to hyperglycemia and hyperinsulinemia, which increase aerobic glycolysis ( the Warburg effect), thereby also contributing to tumor development . 

One of the proteins involved in the Warburg effect in tumor cells is GLUT12, an insulin-responsive glucose transporter whose expression is increased in breast tumors. Bioinformatics tools confirm that high GLUT12 expression is associated with poorer survival in breast cancer patients. Other programs of study studies demonstrate that inhibition of the transporter in in vitro models reduces tumor development . Furthermore, GLUT12 expression increases in breast cancer cell lines in the presence of estrogen and EGF, and with high glucose levels in the culture medium; and in adipocyte and enterocyte cell lines, upon stimulation by the pro-inflammatory cytokine TNF-α and under hypoxic conditions. 

Tumor-associated adipocytes (TAA) are one of the most important components of the tumor microenvironment in breast cancer due to their interaction with tumor cells. In preliminary programs of study from our group, conducted on breast cancer tumor samples, high expression of GLUT12 was observed in tumor cells adjacent to TAS. However, GLUT1, a transporter known to be important in solid tumors, is barely expressed in that area of the tumor.

Since GLUT12 is a transporter whose expression and activity are increased by insulin and high concentrations of extracellular glucose, and since obesity can be accompanied by hyperglycemia and hyperinsulinemia, in this work we set the following objectives:

1.- To investigate, in tumor samples from postmenopausal patients with luminal-subtype breast cancer, whether there are differences in GLUT12 expression between normal-weight and overweight/obese patients, in a retrospective study.

2.- To conduct a pilot study to investigate the effects of high GLUT12 expression in tumor cells on contact with tumor-associated adipocytes, obtained from lumpectomies of postmenopausal patients with luminal-subtype breast cancer who are overweight or obese, in a prospective study.

3. Analyze the potential association between tumor GLUT12 expression and the following tumor and patient characteristics programs of study: tumor oncogenic markers, markers of the adipose tumor microenvironment, plasma biomarkers, and clinical characteristics of the patients.