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BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population.
(OXFORD UNIV PRESS, 2019-05-01)
BACKGROUND: BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1-3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive ...
Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.
(BMC, 2019-04-30)
BACKGROUND: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, ...
Molecular Residual Disease and Adjuvant Trial Design in Solid Tumors.
(AMER ASSOC CANCER RESEARCH, 2019-10)
Advances in diagnosis and treatment have resulted in a high rate of survival for many patients with early-stage cancers. However, identifying who is at ongoing risk of relapse remains of high priority to direct subsequent ...
Identification and Characterization of Novel Receptor-Interacting Serine/Threonine-Protein Kinase 2 Inhibitors Using Structural Similarity Analysis.
(AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS, 2018-05-01)
Receptor-interacting protein kinase 2 (RIP2 or RICK, herein referred to as RIPK2) is linked to the pathogen pathway that activates nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) and autophagic activation. ...
Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).
(ELSEVIER, 2019-03-01)
Better knowledge of the tumor genomic landscapes has helped to develop more effective targeted drugs. However, there is no tool to interpret targetability of genomic alterations assessed by next-generation sequencing in ...
Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation.
(AMER SOC CLINICAL INVESTIGATION INC, 2019-08-08)
Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are ...
C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.
(WILEY, 2019-09-16)
Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome-wide ...
Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma.
(AMER ASSOC CANCER RESEARCH, 2019-04-15)
Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility ...
The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.
(CELL PRESS, 2019-10-22)
Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the ...
Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF-TIMI 48 Trial.
(WILEY, 2017-08-11)
BACKGROUND: The impact of different types of extracranial bleeding events on health-related quality of life and health-state utility among patients with atrial fibrillation is not well understood. METHODS AND RESULTS: The ...