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A small, orally bioavailable molecule targeting an enzyme in the endoplasmic reticulum (ER) blocks protein folding, induces ER stress and results in tumor cell death. This discovery provides new insights to develop targeted strategies for treating solid tumors, including breast, brain, pancreatic and ovarian tumors. The study shows, the candidate drug is effective against estrogen receptor-positive breast cancers, TNBC, and other solid tumor types with elevated ER stress, without any adverse effects on normal human or animal cells.
High-grade serous ovarian carcinoma (HGSOC) creates an immunosuppressive tumor microenvironment that renders this form of malignancy insensitivity to checkpoint inhibitor immunotherapies. A new study shows combining an oral inhibitor of a gene that encodes a focal adhesion kinase that is elevated in nearly 70% of patients with HGSOC, together with an antibody that blocks the TIGIT immunoreceptor’s function, generates a significant antitumor response and increased survival time of a mouse model of the lethal cancer.
SP9, an experimental drug that is a stapled peptide that can be inhaled, could help patients with muco-obstructive lung diseases. A stapled peptide is a new therapeutic modality where modified amino acids bind with increased stability to a target protein due to hydrocarbon cross bridges that maintain the rigidity of the structure. The drug reduces airway mucus by preventing excessive and rapid secretion of mucin into the airducts. A new multi-center collaborative study shows SP9 enters airway epithelial cells and blocks ATP-induced mucin secretion in IL-13 primed cells in vitro and in mice.
Metastatic melanoma cells recovered from human brains and grown in tissue cultures make roughly three times as much amyloid beta as cancer cells that have spread to other parts of the body, a new study finds. The study shows treatment of mouse models of melanoma brain metastasis with a pharmacological inhibitor that reduces levels of amyloid beta in the brain, decreases the size of brain melanoma metastases by about half.
A new study shows TAK-981, a potent and selective inhibitor of SUMOylation, induces IFN1 signaling and protects the IFN1 pathway from inactivation within tumors. The inhibitor activates T cells and dendritic cells that present antigens to the adaptive immune system, in both mouse models and in cell lines. The activity of the potential cancer drug depends on the IFN1 pathway and adaptive immunity to suppress tumor growth. Combined with anti-PD1 antibody TAK-981 demonstrates prolonged survival in tumor-bearing mice and increased activation of natural killer cells and CD8 expressing T cells.
A new convection-enhanced macroencapsulation device (ceMED) designed by bioengineers from Brigham and Women’s Hospital, Harvard University, and the University of Massachusetts Medical School offers the potential of faster and more effective treatment for people with type 1 diabetes. Whereas traditional MEDs rely on diffusion, the new MED uses convection to create a continuous flow of nutrients through the capsule improving the number of cells that can be accommodated in each cartridge and increasing their survival, glucose sensitivity and insulin secretion.
Goblet cells that line the major airways in the lungs and produce protective mucus in healthy lungs, are abnormally increased in number in lung diseases resulting in excessive mucus secretion. A new study from scientists at Boston University identify regulatory signals that determine the fate of progenitor cells that produce these goblet cells. Targeting these regulatory signals may provide therapeutic directions for restricting the production of goblet cells in a number of lung diseases such as asthma, COPD (Chronic obstructive pulmonary disease), cystic fibrosis, and chronic bronchitis.