Results 211 to 220 of about 6,810,448 (328)

CDK11 inhibition induces cytoplasmic p21WAF1 splice variant by p53 stabilisation and SF3B1 inactivation

open access: yesMolecular Oncology, EarlyView.
CDK11 inhibition stabilises the tumour suppressor p53 and triggers the production of an alternative p21WAF1 splice variant p21L, through the inactivation of the spliceosomal protein SF3B1. Unlike the canonical p21WAF1 protein, p21L is localised in the cytoplasm and has reduced cell cycle‐blocking activity.
Radovan Krejcir   +12 more
wiley   +1 more source

The rapidly growing landscape of RAS inhibitors: from selective allele blockade to broad inhibition strategies

open access: yesMolecular Oncology, EarlyView.
RAS‐targeted therapies have become a clinical reality. Although promising results in patients have been achieved, there are still challenges ahead such as coping with drug resistance. Here we summarize selected RAS inhibitors targeting either individual KRAS mutant isoforms (KRASG12C, KRASG12D, KRASG12V) or exhibiting a wider inhibitory spectrum ...
Matthias Drosten, Mariano Barbacid
wiley   +1 more source

A guide to reactive oxygen species in tumour hypoxia: measurement and therapeutic implications

open access: yesMolecular Oncology, EarlyView.
Hypoxia reshapes tumour redox landscapes by altering compartmental ROS production (mitochondria, NOX, ER, peroxisomes). Accurate interpretation requires oxygen‐contextualised measurement (live biosensors, chemical probes, EPR, LC–MS) and awareness of artefacts (reoxygenation, probe specificity).
Lina Hacker   +3 more
wiley   +1 more source

Class IIa HDACs forced degradation allows resensitization of oxaliplatin‐resistant FBXW7‐mutated colorectal cancer

open access: yesMolecular Oncology, EarlyView.
HDAC4 is degraded by the E3 ligase FBXW7. In colorectal cancer, FBXW7 mutations prevent HDAC4 degradation, leading to oxaliplatin resistance. Forced degradation of HDAC4 using a PROTAC compound restores drug sensitivity by resetting the super‐enhancer landscape, reprogramming the epigenetic state of FBXW7‐mutated cells to resemble oxaliplatin ...
Vanessa Tolotto   +13 more
wiley   +1 more source

In vitro models of cancer‐associated fibroblast heterogeneity uncover subtype‐specific effects of CRISPR perturbations

open access: yesMolecular Oncology, EarlyView.
Development of therapies targeting cancer‐associated fibroblasts (CAFs) necessitates preclinical model systems that faithfully represent CAF–tumor biology. We established an in vitro coculture system of patient‐derived pancreatic CAFs and tumor cell lines and demonstrated its recapitulation of primary CAF–tumor biology with single‐cell transcriptomics ...
Elysia Saputra   +10 more
wiley   +1 more source

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