# Roles of ADP-Ribosyltransferases in Cancer

## TL;DR

ADP-ribosyltransferases (ARTs) influence cancer processes like DNA repair and immune evasion, and could be important targets for cancer therapy.

## Contribution

This review summarizes the roles of ARTs in cancer and highlights current knowledge on specific inhibitors and therapeutic potential.

## Key findings

- ART1 and ART3 modulate the PI3K/AKT pathway, affecting tumor growth and immune evasion.
- PARP1 and PARP2 are clinically validated targets in cancers with homologous recombination deficiency.
- PARP inhibitors like olaparib and niraparib are FDA-approved and show clinical efficacy.

## Abstract

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.