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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 ...
RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.
(NATURE PORTFOLIO, 2022-09-26)
Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response ...
Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal.
(CELL PRESS, 2018-04-19)
Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with ...
Up-front cell-free DNA next generation sequencing improves target identification in UK first line advanced non-small cell lung cancer (NSCLC) patients.
(ELSEVIER SCI LTD, 2022-08-01)
BACKGROUND: Genomic sequencing is necessary for first-line advanced non-small cell lung cancer (aNSCLC) treatment decision-making. Tissue next generation sequencing (NGS) is standard but tissue quantity, quality, and ...
Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.
(LIPPINCOTT WILLIAMS & WILKINS, 2021-10-01)
PURPOSE: Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently ...
Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer.
(TAYLOR & FRANCIS LTD, 2022-01-02)
INTRODUCTION: Amivantamab is a monoclonal bispecific anti-EGFR-MET antibody that is the first targeted therapy to be approved for non-small cell lung cancer (NSCLC) patients harboring EGFR exon 20 insertion mutations ...