Functional ex vivo assay to select Homologous Recombination deficient breast tumors for PARP inhibitor treatment Running title: Functional assay for PARP inhibitor treatment
نویسندگان
چکیده
Departments of Genetics, Pathology, Radiation Oncology, Medical Oncology and Cancer Genomics Center Netherlands, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands Departments of Toxicogenetics and Human Genetics, Leiden University Medical Center, Leiden, The Netherlands AstraZeneca, iMed Oncology, Macclesfield, Cheshire, United Kingdom # Deceased
منابع مشابه
Functional ex vivo assay to select homologous recombination-deficient breast tumors for PARP inhibitor treatment.
PURPOSE Poly(ADP-ribose) polymerase (PARP) inhibitors are promising targeted treatment options for hereditary breast tumors with a homologous recombination (HR) deficiency caused by BRCA1 or BRCA2 mutations. However, the functional consequence of BRCA gene mutations is not always known and tumors can be HR deficient for other reasons than BRCA gene mutations. Therefore, we aimed to develop a fu...
متن کاملPersonalized Medicine and Imaging Functional Ex Vivo Assay to Select Homologous Recombination–Deficient Breast Tumors for PARP Inhibitor Treatment
Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors are promising targeted treatment options for hereditary breast tumors with a homologous recombination (HR) deficiency caused by BRCA1 or BRCA2 mutations. However, the functional consequence of BRCA genemutations is not always known and tumors can be HR deficient for other reasons than BRCA gene mutations. Therefore, we aimed to develop a fu...
متن کاملTherapeutic targeting and patient selection for cancers with homologous recombination defects.
INTRODUCTION DNA double-strand breaks (DSBs) are toxic DNA lesions that can be repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). Mutations in HR genes elicit a predisposition to cancer; yet, they also result in increased sensitivity to certain DNA damaging agents and poly (ADP-ribose) polymerase (PARP) inhibitors. To optimally implement PARP inhibitor treatment, it...
متن کاملDevelopment of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors.
PURPOSE Poly(ADP-ribose) polymerase (PARP) inhibitors selectively target homologous recombination (HR)-defective cells and show good clinical activity in hereditary breast and ovarian cancer associated with BRCA1 or BRCA2 mutations. A high proportion (up to 50%) of sporadic epithelial ovarian cancers (EOC) could be deficient in HR due to genetic or epigenetic inactivation of BRCA1/BRCA2 or othe...
متن کاملLoss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors.
UNLABELLED Inhibition of PARP is a promising therapeutic strategy for homologous recombination-deficient tumors, such as BRCA1-associated cancers. We previously reported that BRCA1-deficient mouse mammary tumors may acquire resistance to the clinical PARP inhibitor (PARPi) olaparib through activation of the P-glycoprotein drug efflux transporter. Here, we show that tumor-specific genetic inacti...
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