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Article
Open AccessReal-time detection of 20 amino acids and discrimination of pathologically relevant peptides with functionalized nanopore
Precise identification and quantification of amino acids is crucial for many biological applications. Here we report a copper(II)-functionalized Mycobacterium smegmatis porin A (MspA) nanopore with the N91H subst...
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Article
Open AccessImmune checkpoints HLA-E:CD94-NKG2A and HLA-C:KIR2DL1 complementarily shield circulating tumor cells from NK-mediated immune surveillance
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Article
Structural basis of the subcortical maternal complex and its implications in reproductive disorders
The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly basis for ...
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Article
Open AccessOmicron-included mutation-induced changes in epitopes of SARS-CoV-2 spike protein and effectiveness assessments of current antibodies
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading globally and continues to rage, posing a serious threat to human health and life quality. Antibody th...
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Article
Open AccessSingle-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis
The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer. However, cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogene...
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Article
Open AccessGenome-wide CRISPR-cas9 knockout screening identifies GRB7 as a driver for MEK inhibitor resistance in KRAS mutant colon cancer
Targeting the KRAS pathway is a promising but challenging approach for colorectal cancer therapy. Despite showing potent efficacy in BRAF-mutated melanoma, MEK inhibitors appeared to be tolerated by colorectal...
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Article
Open AccessIntegrin-Src-YAP1 signaling mediates the melanoma acquired resistance to MAPK and PI3K/mTOR dual targeted therapy
Activation of PI3K/AKT pathway is one of the most recurrent resistant mechanisms for BRAF-targeted therapy, and the combination of MAPK and PI3K/AKT inhibitors becomes one of the most promising regimens for BR...
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Article
Targeted degradation of immune checkpoint proteins: emerging strategies for cancer immunotherapy
Cancer immunotherapy using immune-checkpoint blockade has displayed promising clinical effects, but prevalent antibody-based inhibitors face multiple challenges such as low response rate, acquired resistance, ...
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Chapter
Mechanisms of Resistance to Checkpoint Blockade Therapy
Immune checkpoint blockades (ICBs), as a major breakthrough in cancer immunotherapy, target CTLA-4 and the PD-1/PD-L1 axis and reinvigorate anti-tumor activities by disrupting co-inhibitory T-cell signaling. W...
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Article
Author Correction: Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours
In the version of this Article originally published, ‘palmitoyltransferase ZDHHC3 (DHHC3)’ was incorrectly referred to as an ‘acetyltransferase’ rather than an as an ‘acyltransferase’; this has now been correc...
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Article
Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours
Checkpoint blockade therapy targeting the programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 promotes T-cell-mediated immunosurveillance against tumours, and has been associated with ma...
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Article
HIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicity
Expression of programmed cell death 1 (PD-1) ligand 1 (PD-L1) protects tumor cells from T cell–mediated immune surveillance, and immune checkpoint blockade (ICB) therapies targeting PD-1 and PD-L1 have exhibit...
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Article
Open AccessJUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma
A prominent mechanism of acquired resistance to BRAF inhibitors in BRAFV600-mutant melanoma is associated with the upregulation of receptor tyrosine kinases. Evidences suggested that this resistance mechanism is ...
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Article
Therapy-induced tumour secretomes promote resistance and tumour progression
Tumour cells respond to an effective, targeted drug treatment with BRAF, ALK or EGFR kinase inhibitors by inducing a complex network of secreted signals that promote tumour growth, dissemination and metastasis...
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Protocol
Detecting Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma
V600BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression. Despite the fact that BRAF inhibitors (B...
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Article
MDM4 is a key therapeutic target in cutaneous melanoma
Although loss-of-function p53 alterations are widespread in many tumors, melanomas typically do not harbor TP53 mutations. This report uncovers upregulation of MDM4 as a frequent trait of melanomas that contribut...
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Article
Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance
The development of acquired drug resistance hampers the long-term success of B-RAF inhibitor therapy for melanoma patients. Here we show V600EB-RAF copy-number gain as a mechanism of acquired B-RAF inhibitor resi...
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Article
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Although clinical trials have shown that RAF inhibitors prolong the survival of patients with BRAF-mutant melanoma, resistance inevitably develops; resistance is shown here to be frequently mediated by the exp...
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Article
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Clinical trials in melanoma patients carrying B-RAF gene mutations have shown promising results with the B-RAF kinase inhibitor PLX4032, but many patients go on to become resistant. Two papers now uncover possibl...
