Recent submissions
Now showing items 1-20 of 3939
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Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.
(2018-01)Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically ... -
CancerGD: a resource for identifying and interpreting genetic dependencies in cancer
(2016-10-26)Abstract Genes whose function is selectively essential in the presence of cancer associated genetic aberrations represent promising targets for the development of precision therapeutics. Here we present CancerGD ( ... -
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors.
(2017-09)Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as BRCA2 HRR defects confer synthetic lethality to PARP inhibitors (PARPi) ... -
Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination.
(2019-08)Ubiquitin-conjugating enzymes (E2s) govern key aspects of ubiquitin signaling. Emerging evidence suggests that the activities of E2s are modulated by posttranslational modifications; the structural underpinnings, however, ... -
Immune Cell Associations with Cancer Risk.
(2020-07)Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in ... -
Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.
(2020-08)Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to ... -
SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells.
(2020-09-10)SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. ... -
Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance.
(2020-07-22)Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This ... -
The complete structure of the human TFIIH core complex.
(2019-03-12)Transcription factor IIH (TFIIH) is a heterodecameric protein complex critical for transcription initiation by RNA polymerase II and nucleotide excision DNA repair. The TFIIH core complex is sufficient for its repair ... -
The cryoelectron microscopy structure of the human CDK-activating kinase
<jats:p>The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by phosphorylating ... -
CRC COVID: Colorectal cancer services during COVID-19 pandemic. Study protocol for service evaluation.
(2020-01)Introduction:COVID-19 has had an impact on the provision of colorectal cancer care. The aim of the CRC COVID study is to describe the changes in colorectal cancer services in the UK and USA in response to the pandemic and ... -
Regulatory roles for SOX11 in development, stem cells and cancer
(Elsevier BV, 2020-06) -
Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours.
(2020-09-03)OBJECTIVE:A comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to identify ... -
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma.
(2020-08-23)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. ... -
Distinct Levels of Reactive Oxygen Species Coordinate Metabolic Activity with Beta-cell Mass Plasticity.
(2017-06-26)The pancreatic beta-cells control glucose homeostasis by secreting insulin in response to nutrient intake. The number of beta-cells is under tight metabolic control, as this number increases with higher nutrient intake. ... -
Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study.
(2020-08-27)OBJECTIVE:To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the ... -
Review: The HSP90 molecular chaperone—an enigmatic ATPase
(Wiley, 2016-08)