Roles of ADP-Ribosyltransferases in Cancer

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• ADP-ribosyltransferases (ARTs) regulate critical cancer processes like DNA repair, transcription, immune response, and treatment resistance.
• The clostridial toxin-like ADP-ribosyltransferase (ARTC) and diphtheria toxin-like ADP-ribosyltransferase (ARTD) families are vital for genomic stability through protein modification (MARylation/PARylation).
• ARTs represent promising therapeutic targets and potential biomarkers in cancer management.

Purpose of the Study:

• To review the roles of ARTC and ARTD enzymes in cancer.
• To explore current knowledge on specific ART inhibitors.
• To highlight ongoing research in ART-targeted cancer therapies.

Main Methods:

• A literature search was conducted in PubMed and Google Scholar.
• Studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer were identified.

Main Results:

• ART1 and ART3 (ARTC family) modulate the PI3K/AKT pathway, affecting angiogenesis, tumor growth, and CD8+ T-cell apoptosis.
• PARP1 and PARP2 (ARTD family) are activated by DNA single-strand breaks and are validated targets in BRCA1/2-mutated cancers.
• PARP inhibition demonstrates synthetic lethality and clinical efficacy, with four FDA-approved inhibitors (olaparib, niraparib, rucaparib).

Conclusions:

• PARP inhibitors offer effective treatment for specific cancers, exemplifying synthetic lethality.
• Selective inhibitors for ARTs are underexplored, presenting a significant area for future drug development.
• Future research aims to overcome PARP inhibitor resistance, enhance patient selection via biomarkers, and expand ART-targeted therapeutic strategies.