Title:DNA Base Excision Repair: The Achilles' Heel of Tumour Cells and their Microenvironment?
Volume: 23
Issue: 32
Author(s): Mattia Poletto *, Arnaud J. Legrand *Grigory L. Dianov*
Affiliation:
- CRUK and MRC Oxford Institute for Radiation Oncology, University of Oxford, Department of Oncology, Old Road Campus Research Building, OX37DQ Oxford,United Kingdom
- CRUK and MRC Oxford Institute for Radiation Oncology, University of Oxford, Department of Oncology, Old Road Campus Research Building, OX37DQ Oxford,United Kingdom
- CRUK and MRC Oxford Institute for Radiation Oncology, University of Oxford, Department of Oncology, Old Road Campus Research Building, OX37DQ Oxford,United Kingdom
Keywords:
Base Excision Repair, Inhibitors, DNA Damage, Cancer, enzymes, anti-cancer therapy.
Abstract: Our current understanding of cancer suggests that every tumour has individual features. Approaches to
cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting
cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system that is
responsible for maintaining genome integrity. The BER pathway prevents the occurrence of disease, including
cancer, by constantly repairing DNA base lesions and DNA single strand breaks caused by endogenous and exogenous
mutagens. BER is an important DNA repair system for cancer cell survival, as it can affect both chemoand
radio-resistance of tumours. Variations in BER capacity are likely responsible for a number of cases of sporadic
cancer and may also modulate cancer sensitivity and resistance to therapeutic treatments. For these reasons,
it is broadly accepted that targeting BER enzymes might be a promising approach to personalised anti-cancer
therapy. However, recent advances in both treatment strategies and the comprehension of cancer development call
for a better understanding of the consequences of BER inhibition. Indeed, the impact on both the tumour microenvironment
and healthy tissues is still unclear. This review will summarise the current status of the approaches
exploiting BER targeting, describing the most promising small molecule inhibitors and synthetic lethality strategies,
as well as potential limitations of these approaches.
