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European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer.
(ELSEVIER, 2022-03-01)
BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers ...
Resistance to DNA repair inhibitors in cancer.
(WILEY, 2022-05-14)
The DNA damage response (DDR) represents a complex network of proteins which detect and repair DNA damage, thereby maintaining the integrity of the genome and preventing the transmission of mutations and rearranged chromosomes ...
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.
(NATURE PORTFOLIO, 2022-01-01)
Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using ...
A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.
(SPRINGERNATURE, 2023-09-01)
Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, ...
Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.
(ELSEVIER, 2022-08-01)
BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ...
ATARI trial: ATR inhibitor in combination with olaparib in gynecological cancers with ARID1A loss or no loss (ENGOT/GYN1/NCRI).
(BMJ PUBLISHING GROUP, 2021-11-01)
BACKGROUND: ARID1A (AT-rich interactive domain containing protein 1A) loss-of-function mutations have been reported in gynecological cancers, including rarer subtypes such as clear cell carcinoma. Preclinical studies ...
Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance.
(AMER ASSOC CANCER RESEARCH, 2022-10-14)
PURPOSE: PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, and prostate cancers. Multiple PARPi resistance ...
Systemic Therapy for Hereditary Breast Cancers.
(W B SAUNDERS CO-ELSEVIER INC, 2023-02-01)
Approximately 5% to 10% of all breast cancers are hereditary; many of which are caused by pathogenic variants in genes required for homologous recombination, including BRCA1 and BRCA2. Here we discuss systemic treatment ...
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A.
(NATURE PUBLISHING GROUP, 2016-12-13)
Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ...
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as BRCA2 HRR defects confer synthetic lethality to PARP inhibitors (PARPi) ...