Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer

Giorgia Colombo; Edoardo Luigi Maria Gelardi; Federica Carolina Balestrero; Marianna Moro; Cristina Travelli; Armando A Genazzani

doi:10.3389/fphar.2021.758320

Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer

Front Pharmacol. 2021 Nov 22:12:758320. doi: 10.3389/fphar.2021.758320. eCollection 2021.

Authors

Giorgia Colombo¹, Edoardo Luigi Maria Gelardi², Federica Carolina Balestrero¹, Marianna Moro¹, Cristina Travelli³, Armando A Genazzani¹

Affiliations

¹ Department of Pharmaceutical Sciences, Università Del Piemonte Orientale, Novara, Italy.
² Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy.
³ Department of Drug Sciences, Università Degli Studi di Pavia, Pavia, Italy.

Abstract

Tumour cells modify their cellular metabolism with the aim to sustain uncontrolled proliferation. Cancer cells necessitate adequate amounts of NAD and NADPH to support several enzymes that are usually overexpressed and/or overactivated. Nicotinamide adenine dinucleotide (NAD) is an essential cofactor and substrate of several NAD-consuming enzymes, such as PARPs and sirtuins, while NADPH is important in the regulation of the redox status in cells. The present review explores the rationale for targeting the key enzymes that maintain the cellular NAD/NADPH pool in colorectal cancer and the enzymes that consume or use NADP(H).

Keywords: ALDH = aldehyde dehydrogenase; CD38; NAD; NADPH; NAMPT (nicotinamide phosphoribosyltransferase); PARP; isocitrate dehydrogenase (IDH); sirtuins.

Publication types

Review