The biological and pharmacological connections between diabetes and various types of cancer

Wang, Xuechang; Ding, Suming

doi:10.1016/j.prp.2021.153641

Cited by 12 publications

(12 citation statements)

References 80 publications

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“…Since then, an increasing number of studies have shown that diabetes can increase the risk of various malignant tumors ( 37 – 39 ). Diabetes and tumors have common risk factors, including age, sex, diet and smoking and their onset is related to the insulin/insulin-like growth factor (IGF) pathway ( 40 ). Patients with diabetes are prone to develop tumors.…”

Section: Metformin As An Antitumor Candidate Drugmentioning

confidence: 99%

Metformin: A promising drug for human cancers (Review)

Huang

Zhao

et al. 2022

Oncol Lett

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Small-molecule chemical drugs are of great significance for tumor-targeted and individualized therapies. However, the development of new small-molecule drugs, from basic experimental research and clinical trials to final application in clinical practice, is a long process that has a high cost. It takes at least 5 years for most drugs to be developed in the laboratory to prove their effectiveness and safety. Compared with the development of new drugs, repurposing traditional non-tumor drugs can be a shortcut. Metformin is a good model for a new use of an old drug. In recent years, the antitumor efficacy of metformin has attracted much attention. Epidemiological data and in vivo , and in vitro experiments have shown that metformin can reduce the incidence of cancer in patients with diabetes and has a strong antagonistic effect on metabolism-related tumors. Recent studies have shown that metformin can induce autophagy in esophageal cancer cells, mainly by inhibiting inflammatory signaling pathways. In recent years, studies have shown that the antitumor functions and mechanisms of metformin are multifaceted. The present study aims to review the application of metformin in tumor prevention and treatment.

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Section: Metformin As An Antitumor Candidate Drugmentioning

confidence: 99%

Metformin: A promising drug for human cancers (Review)

Huang

Zhao

et al. 2022

Oncol Lett

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“…There is controversy over whether the metabolic syndrome actually drives tumorigenesis or is just a passenger contributing on a case-by-case basis to this process. Epidemiological, clinical and experimental reports support that metabolic syndrome associated with insulin confers an increased risk of developing various cancers, including breast, endometrial, ovarian, colon and prostate cancers, as well as diseases associated with insulin resistance syndrome such as type 2 diabetes ( 21 ). Furthermore, available data suggest a key role for IGFs both as a link between insulin resistance syndrome and cancer, and as a driver of cancer drug resistance associated with metabolic syndrome.…”

Section: Igf-1r Signaling: a Key Link Between Metabolic Syndrome And ...mentioning

confidence: 99%

“…For instance, both diabetic and non-diabetic women with insulin resistance have higher risk to develop breast, endometrial and ovarian cancer, and results from studies in ovarian and cervical cancer suggest that the first-line type 2 diabetes drug and anti-insulin resistance agent metformin is a good candidate in combination therapies for these cancers ( 4 , 9 ). Studies have shown that metformin has antitumor activity in the major gynecologic malignancies through a pleiotropic mechanism involving direct silencing of IGF-1R signaling and indirect silencing of this signaling pathway by targeting its downstream targets, including MAPK and mTOR ( 21 , 22 ). Metformin also induced a G1-cell cycle arrest and apoptosis in EML 4 -ALK(+) lung cancer (H3122) cells partly through the modulation of IGF-1 expression ( 23 ).…”

Section: Igf-1r Signaling: a Key Link Between Metabolic Syndrome And ...mentioning

confidence: 99%

Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential

Kamdje¹,

Etet

Kipanyula

et al. 2022

Front. Endocrinol.

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The tumor microenvironment fuels tumorigenesis and induces the development of resistance to anticancer drugs. A growing number of reports support that the tumor microenvironment mediates these deleterious effects partly by overexpressing insulin-like growth factor 1 (IGF-1). IGF-1 is known for its role to support cancer progression and metastasis through the promotion of neovascularization in transforming tissues, and the promotion of the proliferation, maintenance and migration of malignant cells. Anti-IGF therapies showed potent anticancer effects and the ability to suppress cancer resistance to various chemotherapy drugs in in vivo and in vitro preclinical studies. However, high toxicity and resistance to these agents are increasingly being reported in clinical trials. We review data supporting the notion that tumor microenvironment mediates tumorigenesis partly through IGF-1 signaling pathway. We also discuss the therapeutic potential of IGF-1 receptor targeting, with special emphasis on the ability of IGF-R silencing to overcome chemotherapy drug resistance, as well as the challenges for clinical use of anti-IGF-1R therapies.

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“…However, ovarian carcinoma appears to be an exception, whereby prostasin is overexpressed in ovaries [9,10], and elevated serum prostasin concentration serves as a potential diagnostic marker for ovarian carcinoma [10,11]. There is extensive evidence showing that diabetes is associated with an increased risk of cancer and cancer mortality [12], and the association may be altered to some extent by glucose-lowering treatments [13]. The biological connection between these two conditions is still obscure, but several possible mechanisms have been proposed [13].…”

Section: Introductionmentioning

confidence: 99%

“…There is extensive evidence showing that diabetes is associated with an increased risk of cancer and cancer mortality [12], and the association may be altered to some extent by glucose-lowering treatments [13]. The biological connection between these two conditions is still obscure, but several possible mechanisms have been proposed [13]. Among them, hyperglycaemia-induced epithelial-to-mesenchymal transition is considered to facilitate cancer metastasis [14].…”

Section: Introductionmentioning

confidence: 99%

Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality

Bao

Muhammad

et al. 2022

Diabetologia

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Aims/hypothesis Diabetes is associated with an increased risk of cancer. Prostasin is an epithelial sodium channel stimulator that has been associated with suppression of tumours, glucose metabolism and hyperglycaemia-associated tumour pathology. However, the association between prostasin, diabetes and cancer mortality has not been well investigated in humans. We aim to investigate the associations between plasma prostasin and diabetes, and to explore whether prostasin has an effect on cancer mortality risk in individuals with hyperglycaemia. Methods Plasma prostasin was measured using samples from the Malmö Diet and Cancer Study Cardiovascular Cohort, and statistical analysis was performed from both sex-specific quartiles and per 1 SD. The cross-sectional association between plasma prostasin and diabetes was first studied in 4658 participants (age 57.5 ± 5.9 years, 39.9% men). After excluding 361 with prevalent diabetes, the associations of prostasin with incident diabetes and cancer mortality risk were assessed using Cox regression analysis. The interactions between prostasin and blood glucose levels as well as other covariates were tested. Results The adjusted OR for prevalent diabetes in the 4th vs 1st quartile of prostasin concentrations was 1.95 (95% CI 1.39, 2.76) (p for trend <0.0001). During mean follow-up periods of 21.9 ± 7.0 and 23.5 ± 6.1 years, respectively, 702 participants developed diabetes and 651 died from cancer. Prostasin was significantly associated with the incidence of diabetes. The adjusted HR for diabetes in the 4th vs 1st quartile of prostasin concentrations was 1.76 (95% CI 1.41, 2.19) (p for trend <0.0001). Prostasin was also associated with cancer mortality There was a significant interaction between prostasin and fasting blood glucose for cancer mortality risk (p for interaction =0.022), with a stronger association observed in individuals with impaired fasting blood glucose levels at baseline (HR per 1 SD change 1.52; 95% CI 1.07, 2.16; p=0.019). Conclusions/interpretation Plasma prostasin levels are positively associated with diabetes risk and with cancer mortality risk, especially in individuals with high blood glucose levels, which may shed new light on the relationship between diabetes and cancer. Graphical abstract

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The biological and pharmacological connections between diabetes and various types of cancer

Cited by 12 publications

References 80 publications

Metformin: A promising drug for human cancers (Review)

Metformin: A promising drug for human cancers (Review)

Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential

Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality

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