XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib
Institution: University of Nottingham
Corresponding Researcher: Srinivasan Madhusudan
Data Link(s): The authors confirm the data that has been used in this work is available on reasonable request.
Keyword(s): ATM, ATR, AZ31, AZD1775, AZD6738, DNA repair, PARP, Wee1, XRCC1, olaparib, synthetic lethality, triple negative breast cancer
Summary
PARP inhibitor (PARPi) monotherapy is a new strategy in BRCA germ-line deficient triple negative breast cancer (TNBC). However, not all patients respond, and the development of resistance limits the use of PARPi monotherapy. Therefore, the development of alternative synthetic lethality strategy, including in sporadic TNBC, is a priority. XRCC1, a key player in base excision repair, single strand break repair, nucleotide excision repair and alternative non-homologous end joining, interacts with PARP1 and coordinates DNA repair. ATR, ATM and Wee1 have essential roles in DNA repair and cell cycle regulation.
