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Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-08-01)
It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ...
Comparison of BEAMing and Droplet Digital PCR for Circulating Tumor DNA Analysis.
(AMER ASSOC CLINICAL CHEMISTRY, 2019-11-01)
BACKGROUND: Circulating tumor DNA (ctDNA) assays are increasingly used for clinical decision-making, but it is unknown how well different assays agree. We aimed to assess the agreement in ctDNA mutation calling between ...
Measuring Clonal Evolution in Cancer with Genomics.
(ANNUAL REVIEWS, 2019-08-31)
Cancers originate from somatic cells in the human body that have accumulated genetic alterations. These mutations modify the phenotype of the cells, allowing them to escape the homeostatic regulation that maintains normal ...
BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
(ELIFE SCIENCES PUBLICATIONS LTD, 2018-07-10)
The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding ...
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
(NATURE PORTFOLIO, 2018-08-09)
Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered ...
Combined targeting of MEK and the glucocorticoid receptor for the treatment of RAS-mutant multiple myeloma.
(BMC, 2020-03-30)
BACKGROUND: Multiple myeloma (MM) remains incurable despite recent therapeutic advances. RAS mutations are frequently associated with relapsed/refractory disease. Efforts to target the mitogen-activated protein kinase ...
Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.
(NATURE PUBLISHING GROUP, 2020-02-28)
The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated ...
Evolutionary dynamics of neoantigens in growing tumors.
(NATURE PORTFOLIO, 2020-10-01)
Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of ...
A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
(NATURE PUBLISHING GROUP, 2020-06-26)
Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for ...
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
(NATURE PORTFOLIO, 2021-02-17)
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in ...