# Consequences of Glucose Enriched Diet on Oncologic Patients
### Role of Sugar in Cancer Metabolism
#### 1.2.5 Dietary Changes for Effective Cancer Therapy
The tumor suppressor PTEN is inhibited, and mutations in the PIK3 CA and AKT kinase gene clusters activate the PI3K pathway. Stimulation of PI3K signaling by mutations or by insulin activates mTORC1, which lowers autophagy and enhances anabolic activity, biomass accumulation, and proliferation. As a result, the molecular connections between oncogenic signaling, glucose consumption, and blood insulin have been fully described. Additionally, chronically high insulin levels are connected to an increased risk of cancer, such as those reported in people with obesity and/or diabetes. Though additional factors beyond glucose and insulin are expected to play a pro-tumorigenic role in people with diabetes and obesity, insulin and, by proxy, glucose in the diet contribute to the start of cancer and thus, could also be the objective of cancer prevention [70]. The most tested glucose-lowering dietary restriction strategy is caloric restriction, sometimes termed dietary restriction. These diets decrease overall calorie intake by many degrees and result in a drop in blood glucose. For instance, in a human research with  
Figure 3: Summary of chemotherapy and derived synergistic cancer therapy. The different items are shown, such as anticancer immune response, cancer-specific toxicity, starvation, and drug-based therapy and how these affect cell tumors. 18 participants, a 15% decrease in blood glucose was observed following a 50% decrease in total calorie intake. However, they also have considerably broader metabolic effects. Dietary or calorie restriction, while probably advantageous for cancer patients in terms of glucose deprivation to tumors, is not optimal as a suggested diet for patients, as they may affect the general physical state of patients and they are difficult to adhere to. Perchance, a diet that is poor in glucose but has a normal caloric value (an isocaloric diet), such as the ketogenic diet, is a better technique [73]. The ketogenic diet, which is high in fat but low in carbohydrates, may inhibit the progression of cancer. A 30% drop in blood glucose was reached in persons after an isocaloric diet where carbs made up just 8% of the total caloric intake. The ketogenic diet boosts ketone bodies, which are not absorbed by many cancer cells but offer energy to the brain and other tissues. The ketogenic diet is likely most useful when food consumption is controlled and portioned out, allowing the patient to consume just a regular amount of calories. Mechanically, the ketogenic diet reduces circulation of insulin [70], which diminishes activity in pro-proliferative signaling pathways mTORC1 and PI3K and can also exacerbate oxidative stress in cancer cells [70; 73]. Restricting carbs has less of an influence on the proliferation of cancer cells that have PI3K pathway mutations. Although these cells still need glucose for sustenance, the downstream signaling of PI3K is constitutively active, rendering them resistant to the signaling implications of glucose restriction. These results underscore the crucial role of systemic glucose as an insulin-dependent initiator of the PI3K pathway and suggest that blocking this mechanism will limit glucose tumor-promoting actions and effectively impede tumor growth. This method shows potential for patients with cancers that possess mutations in the PIK3C genes, due to the tumors' addiction to insulin signaling. Nevertheless, since most cancers survive on the proliferative downstream signals of PI3K and insulin and require huge amounts of glucose, this technique could be equally as effective in preventing tumors as non-mutated PI3K. Regrettably, drug-induced PI3K inhibition is surprisingly inefficient since compensatory insulin production confers tolerance to this strategy. In mice, blood insulin levels enhance in a few hours after the suppression of the insulin-PI3K-AKT-mTOR signaling pathways, which allows greater glucose uptake and stimulation of oncogenic PI3K signaling by tumors, avoiding the antitumor effects of the treatment [70].