Search Results
You are looking at 1 - 1 of 1 items for
- Author: Abde Abukdheir x
- Refine by access: All content x
Search for other papers by Olga Lakiza in
Google Scholar
PubMed
Search for other papers by Julian Lutze in
Google Scholar
PubMed
Search for other papers by Alyx Vogle in
Google Scholar
PubMed
Search for other papers by Jelani Williams in
Google Scholar
PubMed
Search for other papers by Abde Abukdheir in
Google Scholar
PubMed
Search for other papers by Paul Miller in
Google Scholar
PubMed
Search for other papers by Chih-Yi ‘Andy’ Liao in
Google Scholar
PubMed
Search for other papers by Sean P Pitroda in
Google Scholar
PubMed
Search for other papers by Carlos Martinez in
Google Scholar
PubMed
Search for other papers by Andrea Olivas in
Google Scholar
PubMed
Search for other papers by Namrata Setia in
Google Scholar
PubMed
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois, USA
Search for other papers by Stephen J Kron in
Google Scholar
PubMed
Ludwig Center for Metastasis Research, University of Chicago, Chicago, Illinois, USA
Search for other papers by Ralph R Weichselbaum in
Google Scholar
PubMed
Search for other papers by Xavier M Keutgen in
Google Scholar
PubMed
Somatic MEN1 mutations occur in up to 50% of pancreatic neuroendocrine tumors (PanNETs). Clinical studies have shown that radiation therapy (IR) is effective in a subset of PanNETs, but it remains unclear why some patients respond better to IR than others. Herein, we study whether MEN1 loss of function increases radiosensitivity of PanNETs and determine its effect on DNA double-strand break (DSB) repair. After creating a MEN1 knockout PanNET cell line, we confirmed reduced DSB repair capacity in MEN1-deficient cells and linked these findings to a defect in homologous recombination, as well as reduced BRCA2 expression levels. Consistent with this model, we found that MEN1 mutant cells displayed increased sensitivity to the highly trapping poly (ADP-ribose) polymerase (PARP) 1 inhibitor talazoparib in vitro. Our results suggest that combining IR with PARP inhibition may be beneficial in patients with PanNETs and MEN1 loss of function.
