Results 161 to 170 of about 3,250,985 (308)

Dual PI3K/AKT and CDK4/6 inhibition reveals selective sensitivity in an SHH medulloblastoma stem cell model

open access: yesMolecular Oncology, EarlyView.
Targeted therapy was evaluated in SHH medulloblastoma using neuroepithelial stem cell (NES) and tumor‐derived NES‐like (tNES) models in 2D monolayers and 3D spheroids. PI3K, AKT, and CDK4/6 inhibitors had minimal effects in NES but markedly reduced viability and growth and induced apoptosis in tNES cells, revealing distinct therapeutic vulnerabilities.
Monika Lukoseviciute   +4 more
wiley   +1 more source

Establishment of a humanized patient‐derived xenograft mouse model of high‐grade serous ovarian cancer for preclinical evaluation of combination immunotherapy

open access: yesMolecular Oncology, EarlyView.
We have established a humanized orthotopic patient‐derived xenograft (Hu‐oPDX) mouse model of high‐grade serous ovarian cancer (HGSOC) that recapitulates human tumor–immune interactions. Using combined anti‐PD‐L1/anti‐CD73 immunotherapy, we demonstrate the model's improved biological relevance and enhanced translational value for preclinical ...
Luka Tandaric   +10 more
wiley   +1 more source

Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer

open access: yesMolecular Oncology, EarlyView.
Dysregulation of the Hippo pathway drives nuclear accumulation of YAP/TAZ, activating stemness‐related transcriptional programs that sustain breast cancer stemness and fuel therapeutic resistance across subtypes, underscoring Hippo signaling as a targetable vulnerability. Figure created and edited with BioRender.com.
Giulia Schiavoni   +11 more
wiley   +1 more source

Deciphering transcriptional plasticity in pancreatic ductal adenocarcinoma reveals alterations in sensory neuron innervation

open access: yesMolecular Oncology, EarlyView.
Pancreatic sensory neurons innervating healthy and PDAC tissue were retrogradely labeled and profiled by single‐cell RNA sequencing. Tumor‐associated innervation showed a dominant neurofilament‐positive subtype, altered mitochondrial gene signatures, and reduced non‐peptidergic neurons.
Elena Genova   +14 more
wiley   +1 more source

Heterozygous loss‐of‐function alleles associate the conserved 3′‐5′ exoribonuclease EXOSC10 with hypersensitivity to the anticancer drug 5‐fluorouracil

open access: yesMolecular Oncology, EarlyView.
EXOSC10, an essential nuclear RNA exosome‐associated 3′‐5′ exoribonuclease, is inhibited by the anticancer drug 5‐fluorouracil (5‐FU), and EXOSC10 depletion increases 5‐FU sensitivity. The colon‐cancer variant EXOSC10S402T, located in a proteolysis motif, is stable and nuclear but nonfunctional in vivo.
Radhika Sain   +10 more
wiley   +1 more source

Transcriptional profiling of circulating extracellular vesicles from prebiopsy prostate cancer patients

open access: yesMolecular Oncology, EarlyView.
RNA profiling of circulating extracellular vesicles (EVs) from blood samples of men undergoing prostate biopsy identifies transcripts associated with clinically significant prostate cancer. Integrative analysis with public tumor datasets links EV‐derived gene signatures to tumor stage and progression‐free survival, highlighting CASP3, XRCC2, and RIT1 ...
Stefan Werner   +14 more
wiley   +1 more source

Adaptor protein CIN85 potentiates the motility of osteosarcoma cells via the Akt/mTOR and MMP2‐COL3A1 axis

open access: yesMolecular Oncology, EarlyView.
CIN85 is highly expressed in osteosarcoma, particularly in metastatic lesions. Its overexpression increases cell migration and Matrigel invasion, while silencing CIN85 suppresses these behaviors. Transcriptome analysis shows that CIN85 regulates MMP2, COL3A1, and Akt/mTOR signaling. Targeting these pathways reverses CIN85‐induced motility, highlighting
Iryna Horak   +10 more
wiley   +1 more source

Interpreting the effects of DNA polymerase variants at the structural level

open access: yesMolecular Oncology, EarlyView.
Using MAVISp and molecular dynamics simulations, we analyzed over 60 000 missense variants in POLE and POLD1 from ClinVar, COSMIC, cBioPortal, and saturation mutagenesis. Identified mechanistic indicators, including stability, binding, and long‐range, enable structural interpretation, providing ACMG‐like evidence for possible reclassification of VUS ...
Matteo Arnaudi   +7 more
wiley   +1 more source

Proteasome inhibitor, ixazomib prevents topoisomerase‐I degradation and reverses irinotecan resistance in colorectal cancer

open access: yesMolecular Oncology, EarlyView.
Ixazomib inhibits proteasome‐mediated degradation of topoisomerase I induced by irinotecan, thereby restoring drug sensitivity and promoting tumor cell death in colorectal cancer. Irinotecan, a topoisomerase I (topoI) inhibitor, is widely used for colorectal cancer, but resistance remains a major clinical challenge.
Yuho Ebata   +10 more
wiley   +1 more source

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