Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option

Abstract

The accumulation of reactive oxygen species (ROS) plays a pivotal role in the development of various diseases, including cancer. Elevated ROS levels cause oxidative stress, resulting in detrimental effects on organisms and enabling tumors to develop adaptive responses. Targeting these enhanced oxidative stress protection mechanisms could offer therapeutic benefits with high specificity, as normal cells exhibit lower dependency on these pathways. MTH1 (mutT homolog 1), a homolog of Escherichia coli's MutT, is crucial in this context. It sanitizes the nucleotide pool, preventing incorporation of oxidized nucleotides, thus safeguarding DNA integrity. This study explores MTH1's potential as a therapeutic target, particularly in cancer treatment, providing insights into its structure, function, and role in disease progression.

Keywords: DNA repair; MTH1; MTH1 inhibitor; therapeutic strategy; tumor.

FIGURE 1

Biological functions of MTH1 (dGTP, Deoxyguanosine triphosphate; dATP, Deoxyadenosine triphosphate; ROS, Reactive Oxygen Species; 8-Oxo-dGTP, 8-oxo-2′-deoxyguanosine-5′-triphosphate; 2-OH-dATP, 2′-Deoxyadenosine-5′-Triphosphate, 2′-OH-Modified; MTH1, MutT Homolog 1; 8-Oxo-dGMP, 8-Oxo-2′-deoxyguanosine-5′-monophosphate; 2-OH-dAMP, 2′-Hydroxy-2′-deoxyadenosine-5′-monophosphate; DNA, Deoxyribonucleic Acid).

FIGURE 2

Role of MTH1 in multiple diseases (OGG1, 8-Oxoguanine DNA Glycosylase 1; PASMCs, Pulmonary Artery Smooth Muscle Cells; α-LA, Alpha-Lipoic Acid; NP, Nucleus Pulposus).

FIGURE 3

Advances in the study of MTH1 in a variety of tumors (NSCLC, Non-Small Cell Lung Cancer. ROS, Reactive Oxygen Species; 8-oxo-dGTPase, 8-oxo-2′-deoxyguanosine triphosphatase; PMS2, Postmeiotic segregation increased 2).