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Suboptimal T-cell Therapy Drives a Tumor Cell Mutator Phenotype That Promotes Escape from First-Line Treatment.
(AMER ASSOC CANCER RESEARCH, 2019-05-01)
Antitumor T-cell responses raised by first-line therapies such as chemotherapy, radiation, tumor cell vaccines, and viroimmunotherapy tend to be weak, both quantitatively (low frequency) and qualitatively (low affinity). ...
PARP Inhibitors for Advanced Prostate Cancer: Validating Predictive Biomarkers.
(ELSEVIER, 2019-10-01)
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 ...
ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.
(NATURE PUBLISHING GROUP, 2019-05-09)
Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug ...
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 ...
Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?
(SPRINGER, 2017-07-01)
Germline TP53 mutation carriers are at high risk of developing a range of cancers. Effective cancer risk management is an important issue for these individuals. We assessed the psychosocial impact in TP53 mutation carriers ...
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 ...
Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.
(MASSACHUSETTS MEDICAL SOC, 2019-07-25)
BACKGROUND: Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions. Erdafitinib, a tyrosine kinase ...
Mutational processes contributing to the development of multiple myeloma.
(NATURE PUBLISHING GROUP, 2019-08-06)
To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are ...
Single cell analysis of clonal architecture in acute myeloid leukaemia.
(NATURE PUBLISHING GROUP, 2019-05-01)
We used single cell Q-PCR on a micro-fluidic platform (Fluidigm) to analyse clonal, genetic architecture and phylogeny in acute myeloid leukaemia (AML) using selected mutations. Ten cases of NPM1c mutant AML were screened ...