Tuesday, January 12, 2016

mTOR and Follicular Lymphoma

New research from Nature Genetics: "Recurrent mTORC1-activating RRAGC Mutations in Follicular Lymphoma."

Genetics is not my field, so it always takes extra effort for me to understand the research in a journal like this, but I'm going to do my best.

Cancer researchers have been focused for a while on "pathways." We know that chemotherapy works by killing off whole cancer cells (plus a bunch of non-cancer cells), and sometimes that works and sometimes it doesn't. As we have learned more about cancer, we have discovered that cells depend on "pathways" to grow and survive -- proteins or enzymes in the cell send signals that turn on switches that allow a bunch of different things to happen. These are "pathways" -- expected paths or steps that the cells need to take to do their jobs.

Cancer researchers have been targeting these pathways. If you can cut off a path or keep a step from happening, then the cell dies. Genetic research looks at the gene mutations that cause problems with these pathways. So in a normal cell, a certain gene allows the pathway that tells the cell to stop growing. But in a cancer cell, a gene might mutate or change in a way that the pathway is shut off, so the cell never gets the signal to stop growing.

And sometimes cancer cells have several mutations working at the same time, so several different pathways are affected.

The researchers who wrote this article are focused on the relationship between RRAGC, a certain gene, and the mTOR pathway. They found that with this particular mutation, the cell can become "resistant to amino acid deprivation." Basically, this pathway is supposed to turn on when it gets the signal that there is enough food for the cell to do its job. But because of the mutation, the cell does its job (dividing and growing) whether there is food or not. You can't starve this type of cancer -- it will grow anyway

The researchers estimate that about 30% of FL patients are affected by this mutation. While this particular mutation is a new discovery, the mTOR pathway has been known for a while, and it is already thought to be connected to several types of cancer, plus autism, Alzheimer's disease, and some other age-related problems. The researchers speculate that some of the mTOR pathway inhibitors currently in use could be effective against Follicular Lymphoma. Or, now that there is a new target, a new inhibitor could be developed.

So this research isn't going to lead to another arrow in the quiver anytime soon, but it is important because it gives us one more small piece of a very large and difficult puzzle. There are lots more pieces to be found, but it's nice to know this one is off the list.

1 comment:

Bob said...

Many of the new immunotherapies target these pathways ... AKT, BTK, PI3K and other all the way through mTOR. They appear very effective but not durable. This may lead researchers to target multiple pathways (several immunotherapies simultaneously). In my research they're still to far downstream. I like to think there may be a way to down regulate ALL these pathways at the same time. Also minimize TNF-alpha, CRP, (inflammatory response mechanisms) reduce serum glucose (IGF-1). One of the interesting areas I've found centers on Intermittent Fasting that does this and fosters autophagy and apoptosis.