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Modeling Therapy Resistance in BRCA1/2-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Although PARP inhibitors target BRCA1- or BRCA2-mutant tumor cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 ...
Synthetic lethality: the road to novel therapies for breast cancer.
(BIOSCIENTIFICA LTD, 2016-10-01)
When the BRCA1 and BRCA2 tumour suppressor genes were identified in the early 1990s, the immediate implications of mapping, cloning and delineating the sequence of these genes were that individuals in families with a BRCA ...
PARP inhibitor combination therapy.
(ELSEVIER SCIENCE INC, 2016-12-01)
In 2014, olaparib (Lynparza) became the first PARP (Poly(ADP-ribose) polymerase) inhibitor to be approved for the treatment of cancer. When used as single agents, PARP inhibitors can selectively target tumour cells with ...
Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer.
(AMER SOC CLINICAL INVESTIGATION INC, 2018-10-01)
BACKGROUND: Understanding the integrated immunogenomic landscape of advanced prostate cancer (APC) could impact stratified treatment selection. METHODS: Defective mismatch repair (dMMR) status was determined by either loss ...
A Four-gene Decision Tree Signature Classification of Triple-negative Breast Cancer: Implications for Targeted Therapeutics.
(AMER ASSOC CANCER RESEARCH, 2019-01-01)
The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterize this heterogeneous disease by combining transcriptomics and genomics data, with the ...
Synthetic Lethality and Cancer - Penetrance as the Major Barrier.
(CELL PRESS, 2018-10-01)
Synthetic lethality has long been proposed as an approach for targeting genetic defects in tumours. Despite a decade of screening efforts, relatively few robust synthetic lethal targets have been identified. Improved genetic ...
Synthetic lethal therapies for cancer: what's next after PARP inhibitors?
(NATURE PUBLISHING GROUP, 2018-06-28)
The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline ...
Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets.
(NATURE PUBLISHING GROUP, 2018-05-22)
Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ...
The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells.
(CELL PRESS, 2018-05-15)
Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration ...
Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers.
(WILEY, 2018-07-20)
ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ...