Advances in NAD-Lowering Agents for Cancer Treatment
| Autor: | Alessio Nencioni, Fiammetta Monacelli, Moustafa Ghanem |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA Repair Nicotinamide phosphoribosyltransferase Preiss–Handler pathway Review Nicotinamide adenine dinucleotide NAPRT chemistry.chemical_compound 0302 clinical medicine Neoplasms Cancer De novo pathway Metabolism NAD NAMPT inhibitors Salvage pathway Vitamin B3 Animals Antineoplastic Agents Biosynthetic Pathways Cell Death Cell Line Tumor Cell Survival Cytokines DNA Damage Humans Niacin Niacinamide Nicotinamide Phosphoribosyltransferase Oxidative Stress TX341-641 chemistry.chemical_classification Tumor Nutrition and Dietetics biology 3. Good health Biochemistry 030220 oncology & carcinogenesis DNA repair Cofactor Cell Line 03 medical and health sciences cancer Nicotinamide Nutrition. Foods and food supply salvage pathway 030104 developmental biology Enzyme chemistry Cancer cell biology.protein NAD+ kinase metabolism Food Science |
| Zdroj: | Nutrients, Vol 13, Iss 1665, p 1665 (2021) Nutrients |
| ISSN: | 2072-6643 |
| Popis: | Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor, but it also acts as a substrate for NAD-consuming enzymes, regulating cellular events such as DNA repair and gene expression. Since such processes are fundamental to support cancer cell survival and proliferation, sustained NAD production is a hallmark of many types of neoplasms. Depleting intratumor NAD levels, mainly through interference with the NAD-biosynthetic machinery, has emerged as a promising anti-cancer strategy. NAD can be generated from tryptophan or nicotinic acid. In addition, the “salvage pathway” of NAD production, which uses nicotinamide, a byproduct of NAD degradation, as a substrate, is also widely active in mammalian cells and appears to be highly exploited by a subset of human cancers. In fact, research has mainly focused on inhibiting the key enzyme of the latter NAD production route, nicotinamide phosphoribosyltransferase (NAMPT), leading to the identification of numerous inhibitors, including FK866 and CHS-828. Unfortunately, the clinical activity of these agents proved limited, suggesting that the approaches for targeting NAD production in tumors need to be refined. In this contribution, we highlight the recent advancements in this field, including an overview of the NAD-lowering compounds that have been reported so far and the related in vitro and in vivo studies. We also describe the key NAD-producing pathways and their regulation in cancer cells. Finally, we summarize the approaches that have been explored to optimize the therapeutic response to NAMPT inhibitors in cancer. |
| Databáze: | OpenAIRE |
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