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PARP Inhibitors - Trapped in a Toxic Love Affair.
It is often the case that when an investigational cancer drug first enters clinical development, its precise mechanism of action is unclear. This was the case for PARP inhibitors (PARPi) used to treat homologous ...
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 ...