The Emerging Role of Cyclin-Dependent Kinase Inhibitors in Treating Diet-Induced Obesity: New Opportunities for Breast and Ovarian Cancers?

被引:7
作者
Benot-Dominguez, Reyes [1 ,2 ]
Cimini, Annamaria [3 ]
Barone, Daniela [4 ]
Giordano, Antonio [1 ,2 ,5 ]
Pentimalli, Francesca [6 ]
机构
[1] Temple Univ, Coll Sci & Technol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
[2] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Philadelphia, PA 19122 USA
[3] Univ Aquila, Dept Life Hlth & Environm Sci, I-67100 Laquila, Italy
[4] IRCCS, Cell Biol & Biotherapy Unit, Fdn G Pascale, Ist Nazl Tumori, I-80131 Naples, Italy
[5] Univ Siena, Dept Med Biotechnol, I-53100 Siena, Italy
[6] LUM Univ, Dept Med & Surg, I-70010 Bari, Italy
基金
欧盟地平线“2020”;
关键词
CDK inhibitors (CDKIs); diet-induced obesity (DIO); ovarian cancer; breast cancer; cell-cycle inhibitors; RB1; CDK4; 6; GROWTH-FACTOR-BETA; CELL-CYCLE; PHASE-II; PREDICTIVE BIOMARKER; MOLECULAR-MECHANISMS; ANTAGONIST PEPTIDE; ENDOCRINE THERAPY; GENE-EXPRESSION; CLINICAL-TRIAL; CDK6; INHIBITOR;
D O I
10.3390/cancers14112709
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary This review aims to provide an outline of the potential use of plant-based foods, nutraceuticals, and derived micronutrients-particularly those typically found in the Mediterranean diet-as anticancer agents, with a focus on their mechanism of action as cyclin-dependent kinase inhibitors (CDKIs) by inactivating the CDK 4/6 pathway and the regulation of the cell-cycle cascade. We discuss the preclinical and pharmacological significance of some already approved CDK blockers as a promising therapeutic approach against breast and ovarian cancers. Overweight and obesity constitute the most impactful lifestyle-dependent risk factors for cancer and have been tightly linked to a higher number of tumor-related deaths nowadays. The excessive accumulation of energy can lead to an imbalance in the level of essential cellular biomolecules that may result in inflammation and cell-cycle dysregulation. Nutritional strategies and phytochemicals are gaining interest in the management of obesity-related cancers, with several ongoing and completed clinical studies that support their effectiveness. At the same time, cyclin-dependent kinases (CDKs) are becoming an important target in breast and ovarian cancer treatment, with various FDA-approved CDK4/6 inhibitors that have recently received more attention for their potential role in diet-induced obesity (DIO). Here we provide an overview of the most recent studies involving nutraceuticals and other dietary strategies affecting cell-cycle pathways, which might impact the management of breast and ovarian cancers, as well as the repurposing of already commercialized chemotherapeutic options to treat DIO.
引用
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页数:25
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