# Consequences of Glucose Enriched Diet on Oncologic Patients
### Role of Sugar in Cancer Metabolism
#### 1.2.1 Sugars in the Diet and Cancer Risk
2.2 Possible Significance of Sugar Transporters in Cancer and Its Connection with Anticancer Therapy  
GLUT1 overexpression has been observed in various human malignancies. Furthermore, as dysregulation of GLUT1 expression may suggest the presence of alterations in a number of signaling pathways, GLUT1 expression levels have also been adversely linked with prognosis. Actually, high levels of glucose uptake, one of the hallmarks of malignant cells, are caused by activated Ras or SRC oncogenes, which are key components in the transmission of many signaling pathways. In this regard, it has been proven that mutations in KRAS or BRAF can cause an increase in glucose absorption and GLUT1 overexpression in colorectal cancer cell lines. Moreover, low glucose levels cause wild-type colorectal cancer cell lines to produce more KRAS mutations, upregulating GLUT1 and increasing glucose uptake as a result. Other important alterations in cancer implicated in GLUT1 overexpression affect the local hypoxic pathway and the expression of the MYC oncogene. Additionally, glucose transporters that are not significantly expressed under normal circumstances might be increased by tumor cells [17; 25; 26; 27; 28; 29; 30; 31; 32; 58; 59]. Similar to GLUT1, cancer cells also use SGLT1 stimulation to boost their glucose uptake and glycolysis, so that cancer cells obtain enough energy to support their expansive growth. Still, there is minimal study on SGLT transporter expression in malignancies. In a pioneering work, the activity or expression of an unknown SGLT cotransporter in the colon cancer cell line HT29 was revealed to be controlled by the supplement/deficit of glucose in the culture. In a more recent work, the expressions of the SGLT1 and SGLT2 genes were investigated by RT-PCR in autopsies of primary lung cancers with their metastatic lesions and normal lung. The expressions of SGLT1 and SGLT2 were observed to be unchanged between matched normal lung tissue and tumor samples. Analyzing the metastatic lesions (in lymph nodes and the liver) of the lung tumors, SGLT2 expression was observed to be much higher in the metastatic sites compared to that in the primary tumors, while SGLT1 expression did not alter. Ref. [17] shows a great way to analyze the expressions of SGLT1 and SGLT2 in lung cancer, even if the type of the sample (autopsies) may limit the value of the results obtained. Furthermore, using an immunohistochemical methodology, the expression of SGLT1 (as well as p53 and BCL2) in pancreatic cancer was examined in order to associate the results acquired with different survival determinants. This article indicates that, in pancreatic adenocarcinomas, SGLT1 overexpression was considerably related with disease-free survival. Furthermore, the enhanced expression of SGLT1 in primary pancreatic tumors was involved with a high expression of Bcl-2 [60; 61; 62]. This prospective investigation proposes that, although it should be tested by a more sensitive approach such as qRT-PCR7, Bcl-2 and SGLT1 are promising predictive biomarkers for pancreatic cancer [17]. Most cancers have elevated expressions of sugar transporters [17] and boosted glycolysis. This occurrence, which occurs even under aerobic conditions, that is, in the presence of enough oxygen to complete mitochondrial respiration, is called the Warburg effect, and it is regarded as a crucial metabolic change during malignant transformation. The biological basis for creating drugs that particularly target cancer cells by pharmacologically deactivating sugar transport and/or glycolysis is supported by the amplified dependence of tumor cells on sugars and the glycolytic pathway to create ATP. Glycolytic inhibitors are generally effective against cancers that demonstrate increased glycolytic activity owing to hypoxic circumstances or mitochondrial abnormalities. These events are generally involved in poor response to conventional treatment and resistance.