New Combo for Follicular Lymphoma?

The Journal of Experimental Medicine has a new piece out called "Frequent Disruption of the RB Pathway in Indolent Follicular Lymphoma Suggests a New Combination Therapy." It's a pretty dense article, but it offers a great payoff.

The authors point out that "loss of cell cycle controls" is a feature of aggressive lymphomas (that is, cells don't realize that they are supposed to die), but that process as well understood in Follicular Lymphoma.

The researchers looked at genetic information from two large froups of Follicular Lymphoma patients, and found that about half of them had a particular problem wih the Retinoblastoma pathway (that's the "RB Pathway" in the title). Retinoblastoma proteins are important in regulating cell cycles. In other words, if they get messed up, then cells don't know when to die. Obviously, this is a problem. Retinoblastoma proteins are controlled by a gene called RB1.

Now, the researchers also noticed that when the RB1 gene is messed up, there is also frequent activity from something called the CDK4, or Cyclin-Dependant Kinase 4. CDK4 is an enzyme that helps in particular stages of cell division. It is also controlled by a particular gene, and when that gene gets messed up, CDK4 can't do its job, and cells don't know when to stop dividing.

So we have two things going on here: cells that can't stop dividing and then not dying. And, of course, we call that cancer.

The researchers suggest that, since we have two processes going on that are controlled by two different genes, an effective way to control them would be to combine CDK4 inhibitors with BCL2 inhibitors. (BCL stands for B-Cell Lymphoma, and is yet another gene that regulates cell death.) They call this combination an "untapped therapeutic opportunity," and say that it is "safe and effective against available models of FL."

So while this combination is effective against a model, it hasn't been tried out in combination yet. However, both CDK4 inhibitors and BCL2 inhibitors do exist already, and have been going through clinical trials for a bunch of different cancers, including some blood cancers.

So this one may be a combo for the future.

I'll say this, though, for the present: I find it fascinating that researchers are able to identify problems on a genetic level and determine how they affect cancer cells. This was all unheard of not so many years ago. The pace that we are coming to understand the way our bodies work is just amazing.

It certainly should make us hopeful for the future.