Novel structured ADAM17 small-molecule inhibitor represses ADAM17/Notch pathway activation and the NSCLC cells' resistance to anti-tumour drugs.

The outcomes of current treatment for non-small cell lung cancer (NSCLC) are unsatisfactory and development of new and more efficacious therapeutic strategies are required. The Notch pathway, which is necessary for cell survival to avert apoptosis, induces the resistance of cancer cells to antitumour drugs. Notch pathway activation is controlled by the cleavage of Notch proteins/receptors mediated by A disintegrin and metalloproteinase 17 (ADAM17); therefore, ADAM17 is a reliable intervention target for anti-tumour therapy to overcome the drug resistance of cancer cells.

Molecular characterization based on tumor microenvironment-related signatures for guiding immunotherapy and therapeutic resistance in lung adenocarcinoma.

Although the role of tumor microenvironment in lung adenocarcinoma (LUAD) has been explored in a number of studies, the value of TME-related signatures in immunotherapy has not been comprehensively characterized. Consensus clustering was conducted to characterize TME-based molecular subtypes using transcription data of LUAD samples. The biological pathways and immune microenvironment were assessed by CIBERSORT, ESTIMATE, and gene set enrichment analysis.

PTK7-Targeting CAR T-Cells for the Treatment of Lung Cancer and Other Malignancies.

In spite of impressive success in treating hematologic malignancies, adoptive therapy with chimeric antigen receptor modified T cells (CAR T) has not yet been effective in solid tumors, where identification of suitable tumor-specific antigens remains a major obstacle for CAR T-cell therapy due to the "on target off tumor" toxicity. Protein tyrosine kinase 7 (PTK7) is a member of the Wnt-related pseudokinases and identified as a highly expressed antigen enriched in cancer stem cells (CSCs) from multiple solid tumors, including but not limited to triple-negative breast cancer, non-small-cell lung cancer, and ovarian cancer, suggesting it may serve as a promising tumor-specific target for CAR T-cell therapy. In this study, we constructed three different PTK7-specific CAR (PTK7-CAR1/2/3), each comprising a humanized PTK7-specific single-chain variable fragment (scFv), hinge and transmembrane (TM) regions of the human CD8α molecule, 4-1BB intracellular co-stimulatory domain (BB-ICD), and CD3ζ intracellular domain (CD3ζ-ICD) sequence, and then prepared the CAR T cells by lentivirus-mediated transduction of human activated T cells accordingly, and we sequentially evaluated their antigen-specific recognition and killing activity and .

Novel small molecule inhibitors of the transcription factor ETS-1 and their antitumor activity against hepatocellular carcinoma.

The transcription factor ETS-1 (E26 transformation specific sequence 1) is the key regulator for malignant tumor cell proliferation and invasion by mediating the transcription of the invasion/migration related factors, e.g. MMPs (matrix metalloproteinases).

Slug Is Associated With Tumor Metastasis and Angiogenesis in Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy among women and usually initiated by the malignant transformation of epithelial cells. The progression of ovarian cancer involves a cascade of events, including tumor cell epithelial-mesenchymal transition (EMT), invasion, migration, and angiogenesis. Slug plays vital roles in the development of motile and invasive manner of cancer cells via EMT progression.

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.

Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling.