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Here is an image of the X-ray crystal structure of the Axl/Gas6 complex where Gas6 domains are green and Axl domains are magenta.

A protein pathway on the cell surface that goes rogue in a wide range of cancers can be blocked with a minimum of side effects, according to a new paper by researchers from Rutgers Cancer Institute of New Jersey.

TAM receptor tyrosine kinases, which are overactive in some of the most aggressive and deadly tumors, are connected to another overexpressed factor, the Gas6 ligand. The new trials in mouse models show the ability to block the pathway, report researchers at the Rutgers Cancer Institute of New Jersey and the Rutgers Robert Wood Johnson Medical School.

The scientists describe the efficacy of blocking the TAM receptors and Gas6 from binding, and therefore stopping the tumors’ spread.

William J. Welsh, one of the scientists from the Cancer Institute, said in a short Q&A released by the school that the team had targeted the receptor sites outside the cells – which meant potentially less side-effects, and more coverage amongst the TAM receptor family (which includes Tyro3, Axl and Mertk).

“Taken together, our work reported in the paper establishes a novel alternative strategy for developing pan-TAM inhibitors that may lead to first-in-class anticancer therapeutics that could be delivered as standalone drugs or in combination with current standard-of-care therapeutics… in particular the latest generation of immune-oncology checkpoint inhibitors,” said Welsh.

The inhibitor factor was first shown through in vitro models with cancer cell lines.

To test their concept in an in-vivo model, lung-cancer tumors were grafted subcutaneously into 24 mice, and the animals were split up into three groups with varying amounts of the inhibitor.

It successfully blocked the tumor from developing through the TAM pathway, the scientists report. The work was also complemented by colleagues at the University of Missouri.

The TAM pathway’s overactivity is connected to cancer pathology. But its underexpression has been connected to autoimmune and chronic inflammatory responses.

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