期刊
PHARMACOLOGICAL RESEARCH
卷 175, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2021.106039
关键词
SGLT2; Diabetes; Hyperglycemia; Cancer; Epigenetics
资金
- Italian Ministry of Health
- Italian Ministry of University and Research (MIUR) [PRIN2017F8ZB89]
- POR Campania FSE 2014-2020 ASSE III
- MIUR, Proof of Concept [POC01_00043]
- Campania Regional Government FASE2: IDEAL
- Campania Regional Government Technology Platform Lotta alle Patologie Oncologiche: iCURE
- VALERE: Vanvitelli per la Ricerca
- EPIGEN-MIUR-CNR
- EPICHEMBIO [CM1406]
- Blueprint [282510]
- Epigenetic Hallmarks of Multiple Sclerosis (acronym Epi-MS) [415, 138]
- [AIRC-17217]
- [MIUR20152TE5PK]
Diabetic patients have an increased cancer risk and higher mortality rate. High blood glucose plays a role in promoting cancer progression. Inflammation is a common feature in both diabetes and cancer patients, and the correlation between high blood glucose and inflammation makes tumor development more susceptible. Glycemic control is crucial in treating diabetes and also has favorable outcomes in cancer.
Epidemiological evidence shows that diabetic patients have an increased cancer risk and a higher mortality rate. Glucose could play a central role in metabolism and growth of many tumor types, and this possible mechanism is supported by the high rate of glucose demand and uptake in cancer. Thus, growing evidence suggests that hyperglycemia contributes to cancer progression but also to its onset. Many mechanisms underlying this association have been hypothesized, such as insulin resistance, hyperinsulinemia, and increased inflammatory processes. Inflammation is a common pathophysiological feature in both diabetic and oncological patients, and inflammation linked to high glucose levels sensitizes microenvironment to tumorigenesis, promoting the development of malignant lesions by altering and sustaining a pathological condition in tissues. Glycemic control is the first goal of antidiabetic therapy, and glucose level reduction has also been associated with favorable outcomes in cancer. Here, we describe key events in carcinogenesis focusing on hyperglycemia as supporter in tumor progression and in particular, related to the role of a specific hypoglycemic drug class, sodium-glucose linked transporters (SGLTs). We also discuss the use of SGLT2 inhibitors as a novel potential cancer therapy. Our metaanalysis showed that SGLT-2 inhibitors were significantly associated with an overall reduced risk of cancer as compared to placebo (RR = 0.35, CI 0.33-0.37, P = 0. 00) with a particular effectiveness for dapaglifozin and ertuglifozin (RR = 0. 06, CI 0. 06-0. 07 and RR = 0. 22, CI 0. 18-0. 26, respectively). Network Medicine approaches may advance the possible repurposing of these drugs in patients with concomitant diabetes and cancer.
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