News of note—Beating I-O resistance by blocking a gene; Unlocking metformin's potential beyond diabetes

Mouse
Inhibiting the gene PAK4 with Karyopharm's KPT-9274 reversed resistance of PD-1 blockade in mouse models of melanoma. (Pixabay)

Karyopharm’s PAK4 blocker overcomes resistance to immuno-oncology drugs in mice
Drugs that inhibit the immune checkpoint PD-1, such as Keytruda, have revolutionized the treatment of many cancers, but some patients become resistant to them. A study from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, could point to new strategies for overcoming immuno-oncology resistance. The UCLA researchers studied biopsies from people with melanoma who received Keytruda and discovered that non-resistant tumors exhibited high expression of the gene PAK4. When they inhibited PAK4 in mice using Karyopharm’s investigational drug KPT-9274, they observed an increase in tumor-specific immune cells and a subsequent reversal of resistance to PD-1 blockade. They published the results in the new journal Nature Cancer. (Release)

How the diabetes drug metformin might do more than just lower glucose
The widely used type 2 diabetes drug metformin is currently being investigated in more than 1,500 clinical trials for its potential to treat a range of diseases, from cancer to heart disease. But how does the drug offer benefits beyond just lowering blood glucose? Scientists from McMaster University discovered that metformin communicates with tissues in the body in a way that causes the liver to secrete the appetite-suppressing protein GDF15, which could result in weight loss. To confirm their suspicion, they deleted the gene that makes GDF15 in mice and observed that the animals did not lose weight after being dosed with metformin. They believe the findings, published in the journal Nature Metabolism, justify the further study of GDF15 and its role in multiple diseases. (Release)

Could CAR-T loaded on metal strips fight solid tumors?
Personalized treatments known as CAR-T cells are on the market to treat blood cancers, but the technology has been difficult to adapt to solid tumors. Scientists at the Fred Hutchinson Cancer Research Center have come up with a new way to deliver CAR-T to tumors. It's a mesh scaffold, about seven times thinner than a human hair, that's made from the same metal used in stents, bone repair and braces to straighten teeth. In a study published in Nature Biomedical Engineering, the researchers described their technique, which involves loading CAR-T cells onto the mesh and implanting them on tumors. They reported that in mouse models of ovarian cancer, the treatment caused tumors to disappear in 10 days. (Release)

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