Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar.
Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia.
Biomolecules. 2022 Oct 28;12(11):1580. doi: 10.3390/biom12111580.
It is a well-accepted fact that obesity and diabetes increase the risk of incidence of different cancers and their progression, leading to a decrease in the quality of life among affected cancer patients. In addition to decreasing the risk of cancers, maintaining a healthy body mass index (BMI)/body weight and/or blood glucose levels within the normal range critically impacts the response to anti-cancer therapy among affected individuals. A cancer patient managing their body weight and maintaining blood glucose control responds better to anti-cancer therapy than obese individuals and those whose blood glucose levels remain higher than normal during therapeutic intervention. In some cases, anti-diabetic/glucose-lowering drugs, some of which are also used to promote weight loss, were found to possess anti-cancer potential themselves and/or support anti-cancer therapy when used to treat such patients. On the other hand, certain glucose-lowering drugs promoted the cancer phenotype and risked cancer progression when used for treatment. Tirzepatide (TRZD), the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide/gastric inhibitory peptide (GIP) agonist, has recently gained interest as a promising injectable drug for the treatment of type 2 diabetes and was approved by the FDA after successful clinical trials (SURPASS 1/2/3/4 and 5, NCT03954834, NCT03987919, NCT03882970, NCT03730662, and NCT04039503). In addition, the reports from the SURMOUNT-1 clinical trial (NCT04184622) support the use of TRZD as an anti-obesity drug. In the current review article, we examine the possibility and molecular mechanisms of how TRZD intervention could benefit cancer therapeutics or increase the risk of cancer progression when used as an anti-diabetic drug in diabetic patients.
肥胖和糖尿病会增加不同癌症的发病风险和进展,导致癌症患者的生活质量下降,这是一个公认的事实。除了降低癌症风险外,保持健康的体重指数(BMI)/体重和/或血糖水平在正常范围内,对受影响个体的癌症治疗反应也有重要影响。与肥胖者和治疗过程中血糖水平仍高于正常水平的个体相比,控制体重和血糖的癌症患者对癌症治疗的反应更好。在某些情况下,一些具有降血糖/降低血糖作用的糖尿病药物本身具有抗癌潜力,在用于治疗此类患者时也支持癌症治疗。另一方面,某些降低血糖的药物在用于治疗时会促进癌症表型并增加癌症进展的风险。胰高血糖素样肽 1(GLP-1)和葡萄糖依赖性胰岛素释放肽/胃抑制肽(GIP)激动剂 Tirzepatide(TRZD)最近作为治疗 2 型糖尿病的有前途的注射药物引起了关注,并在成功的临床试验后获得了 FDA 的批准(SURPASS 1/2/3/4 和 5、NCT03954834、NCT03987919、NCT03882970、NCT03730662 和 NCT04039503)。此外,来自 SURMOUNT-1 临床试验(NCT04184622)的报告支持将 TRZD 用作抗肥胖药物。在本综述文章中,我们研究了 TRZD 干预如何通过作为糖尿病患者的抗糖尿病药物来有益于癌症治疗或增加癌症进展的风险的可能性和分子机制。