Some students I was teaching thought that this might be possible: to engineer the insulin-producing cells with a correctly functioning gene, a type of gene therapy.  While this has been a goal for researchers, and they have successfully made insulin-producing cells in the lab from embryonic stem cells, they are not appropriate for transplant because they do not release the insulin in response to glucose levels.  Plus, the immune system might still recognize these cells as foreign and destroy them.

So a new study is looking at transforming cells of the gut that don’t have a specific job yet.  These cells receive signals throughout the life of an individual to become many different types of cells that are used for normal gut function.  So could they engineer these cells to receive the signals to become insulin-producing cells?  Also, would the cells only release the insulin in response to blood glucose levels?

Two Columbia University researchers have started finding possible answers to these questions.  Once they turned off a gene that normally plays a key role in the fate of a cell, insulin-producing cells were generated.  Having cells in the gut that make insulin can be dangerous if they did not release insulin in response to blood glucose levels, but these “new” gut cells have glucose-sensing receptors to allow them to do just that. Another remarkable feature was that the gene could be turned off either early on in development, or later on in adulthood, so it wouldn’t matter how old the patient was.

The next step is to take the research that has been done on mice so far, and see if they can mimic this in humans with the use of a drug or chemical.  This method will also need to prove to be safe and more effective than current methods of treatment, not just to avoid the burden of daily injections.

Researchers have known for a while that not only are glioblastoma multiforme cells highly resistant to chemotherapy, but they can also deftly migrate away from sites of radiation or surgery, setting up camp and regrowing in other parts of the brain. This means that brain cancer is notoriously difficult to treat and the prognosis is almost always grim.

Last year the New York Times described Hanahan and Weinberg’s Hallmarks of Cancer as follows:

“Through a series of random mutations, genes that encourage cellular division are pushed into overdrive, while genes that normally send growth-restraining signals are taken offline. With the accelerator floored and the brake lines cut, the cell and its progeny are free to rapidly multiply. More mutations accumulate, allowing the cancer cells to elude other safeguards and to invade neighboring tissue and metastasize.”

This is a nice analogy, relating overgrowth of cells paired with lack of cell death (apoptosis) as the accelerator and brakes of a car.

However Amy Keating and colleagues at the University of Colorado Cancer Center focused on the car’s GPS system. They published data in Nature: Oncogene showing that when a receptor tyrosine kinase involved in cancer cell growth, Mer, is switched off, significantly less cancer cells migrate to neighboring tissue in cultured laboratory cells. Keating found that not only does Mer interfere with the molecular signaling pathway, but also the cytoskeletal organization (the structure of the cell).

In other words, the Mer switch interferes with the electrics of the GPS system as well as the steering wheel of the car.

This added to their previous finding that Mer could increase some brain cancer cells’ sensitivity to chemotherapy.

So Mer inhibition could be a “double whammy” approach to treating brain cancer: kill as many cancer cells as possible and stop those remaining from migrating.