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DAISY: picking synthetic lethals from cancer genomes.
(CELL PRESS, 2014-09-08)
A better understanding of genetic interactions in cancer might help identify new therapeutic approaches that exploit the concept of synthetic lethality. Ruppin and colleagues have developed a new computational method, ...
The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate notch signalling.
(IMPACT JOURNALS LLC, 2014-12-15)
CYLD, an ubiquitin hydrolase, has an expanding repertoire of regulatory roles in cell signalling and is dysregulated in a number of cancers. To dissect CYLD function we used a proteomics approach to identify CYLD interacting ...
Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines.
(CELL PRESS, 2016-03-15)
One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase ...
PARP inhibitors: Synthetic lethality in the clinic.
(AMER ASSOC ADVANCEMENT SCIENCE, 2017-03-17)
PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors ...
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 ...
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 ...
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
Directing the use of DDR kinase inhibitors in cancer treatment.
(TAYLOR & FRANCIS LTD, 2017-12-01)
Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different ...
CancerGD: A Resource for Identifying and Interpreting Genetic Dependencies in Cancer.
(CELL PRESS, 2017-07-26)
Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that ...
Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells.
(NATURE PUBLISHING GROUP, 2017-03-01)
We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 ...