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Combining large scale in silico analysis with fragment screening to identify novel, ligandable secondary sites in cancer-associated proteins
(Institute of Cancer Research (University Of London), 2020-01-31)
Proteins often have multiple binding sites involved in interactions with other molecules. The majority of currently approved drugs bind a protein's primary site, the major functional site in the protein. Targeting the ...
Applications of liquid biopsies in metastatic castration resistant prostate cancer
(Institute of Cancer Research (University Of London), 2020-02-29)
Despite many recent advances, treating advanced prostate cancer (PC) remains clinically challenging. The need for vaildated circulating biomarkers is well recognised in almost all cancers, including in PC. Whilst circulating ...
Clinical and co-clinical genomics of paediatric solid tumours with a special focus in DIPG
(Institute of Cancer Research (University Of London), 2020-07-31)
Cure rates for paediatric solid cancers have not improved in the last decade. Delivering precision medicine to stratify patients based on their molecular profiling is a key goal to support existing and upcoming adaptive ...
MAP4K4 Inhibitors
(2020-06-11)
This invention relates to compounds that may be useful as inhibitors of Mitogen-activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4). The invention also relates to the use of these compounds, for example in a method ...
MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma.
(Impact Journals, LLC, 2020-06-09)
This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, ...
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.
(ELSEVIER, 2020-09-01)
BACKGROUND: In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. ...
Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors.
(AMER SOC CLINICAL ONCOLOGY, 2020-06-22)
PURPOSE: Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging ...
Precision genomics for prostate cancer patient stratification
(Institute of Cancer Research (University Of London), 2020-10-31)
Introduction Several unmet needs currently persist in advanced prostate cancers. Despite recent discoveries, such as identification of deficient DNA repair pathways as a key driver of prostate tumour development, relatively ...
History of the Selective Autophagy Research: How Did It Begin and Where Does It Stand Today?
(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2020-01-03)
Autophagy, self-eating, is a pivotal catabolic mechanism that ensures homeostasis and survival of the cell in the face of stressors as different as starvation, infection, or protein misfolding. The importance of the research ...
Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females.
(WILEY, 2020-01-01)
Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the ...