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A specific genetic change called an ALK fusion causes non-small cell lung cancer (NSCLC) in some patients. This abnormality causes the ALK protein to be overactive. These tumors can be treated with ALK inhibitors, but the cancer cells quickly develop resistance. Now, in a new study, researchers from the German Cancer Research Center have demonstrated in mouse and human tumor cells that simultaneous treatment with ALK and SRC inhibitors can improve the therapeutic response of lung cancer cells and delay the development of drug resistance. This combination therapy, which strongly interferes with the protein composition of cancer cells, could improve clinical outcomes in some forms of non-small cell lung cancer. Relevant research results were recently published in Drug Resistance Updates. The paper is titled "Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome."
CDK4/6 inhibitors (CDK4/6i, CDK4/6 inhibitors) can improve the survival rate of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug tolerance and disease progression. Loss-of-function alterations in RB1 confer resistance to CDK4/6i, but optimal therapies for these patients have yet to be developed.
Nuclear factor κB (NF-κB) plays an important role in the occurrence of various human diseases. Various inflammatory signals, including circulating lipopolysaccharides (LPSs), can activate the expression of NF-κB through special receptors. Recently, in a research report titled "Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB" published in the international journal Cell, scientists from Dana-Farber Cancer Institute and other institutions are expected to help develop new targeted therapies to inhibit the activation of NF-κB.
Researchers from Shanghai Jiao Tong University in China recently published a research paper titled "Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers" online in Nature Biomedical Engineering. This study reports the design and performance of a virus-like particle targeting dendritic cells (DCs). The particles feature the Sindbis viral glycoprotein engineered to recognize surface proteins on DCs and package mRNA encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein or herpes simplex virus 1 glycoproteins B and D.
Bejamine Deverman's team at the Broad Institute recently published a research paper titled "An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery" online in Science. The study designed an AAV capsid, BI-hTFR1, that binds to the human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier (BBB). Compared with AAV9, BI-hTFR1 has a higher active transport capacity across the human brain endothelial cell layer and provides a 40-50-fold enhancement of reporter gene expression in the CNS of mice carrying a human TFRC knock-in. This enhanced tropism is CNS specific and is not present in wild-type mice.
Recently, Xiamen University in China published a research paper titled "Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects" in the journal Signal Transduction and Targeted Therapy. This study developed an oncolytic virus, rVSV-LCMVG, that is less likely to induce virus-neutralizing antibodies, and further confirmed that the oncolytic virus can enhance the anti-tumor effect when used in combination with adoptive transfer of T cells or mRNA cancer vaccines.
Recently, in a research report titled "Recurrent mutations in tumor suppressor FBXW7 bypass Wnt/β-catenin addiction in cancer" published in the international magazine Science Advances, scientists from Duke-NUS Medical School and other institutions have revealed why some pancreatic and colorectal cancer patients do not respond to Wnt inhibitors. Wnt inhibitors are a new class of cancer drugs currently under development to treat the above cancers. The findings could not only provide a new cancer therapy target, but also provide a potential screening tool to help identify patients who would benefit from new therapies.
DNA methylation is an important epigenetic mark in mammals. Methylation of cytosines, primarily in the context of CpGs, ensures appropriate regulation of imprinted and tissue-specific genes, silences repetitive elements, and contributes to the function of key functional elements of the genome such as centromeres.
Professor Michael Elowitz of California Institute of Technology and others published a research paper titled "Synthetic protein circuits for programmable control of mammalian cell death" in the top international academic journal Cell. In this study, the research team developed a synthetic protein-level cell death circuit - the Synpoptosis circuit, which regulates cell death execution proteins through hydrolysis, thereby controlling mammalian cell apoptosis and pyroptosis. Furthermore, this circuit can be delivered and passed between cells using virus-like particles (VLPs), providing the basis for engineering synthetic killer cells that induce desired death programs in target cells without self-destruction. Taken together, these results lay the foundation for programmable control of mammalian cell death.
Glioblastoma multiforme (GBM) is the most common and lethal form of primary astrocytic brain tumors and is associated with hypervascularity and heterogeneity. GBM "growth units" consist of glioma stem cells (GSCs), whose transcriptomes range from prothecal cells (PN) to mesenchymal cells (MES), reminiscent of the corresponding GBM subtypes. These characteristics arise from the superposition of differentiation programs and the potential impact of oncogenic mutations.
