Saturday, August 16, 2014

EZH2 Inhibitor for Follicular Lymphoma?

ASH, the American Society for Hematology, has a summer conference on Lymphoma Biology. It ended a couple of days ago. It's much smaller and more focused than the main ASH conference. They also don't make the abstracts and materials public like they do for the main conference. And it doesn't look like there was much about Follicular Lymphoma discussed there.

But I did find this -- a press release from Epizyme, the company that is partnering in creating and testing EPZ-6438, an EZH2 Inhibitor. The presentation focuses on pre-trial and phase 1 trial results. In other words, it's all very early, and very limited -- they only discuss one Follicular Lymphoma patient -- but I think it's worth looking at, since this class of inhibitors seems like it will be a big part of our futures as Follicular Lymphoma patients.

First off, the whole EZH2 Inhibitor thing. EZH2 is the name of a gene that encodes an enzyme, also called EZH2. When there is too much EZH2, a chain reaction is set off. Too much EZH2 enyzme results in the creation of too much histone methylation, a process that leads to bad things happening to some other genes that suppress tumors. [I just erased a paragraph of science-y stuff that I was having trouble following myself. Let's just say this: EZH2 needs to be controlled, because if it isn't, it will allow cells to live for as long as they want to. Next step = cancer.]

EZH2 seems to play a role in a bunch of cancers, both solid and liquid, including some types of Follicular Lymphoma. (Remember -- there isn't just one type of FL. About 22% of Follicular Lymphoma patients have the mutation that is related to EZH2.)

So the EPZ-6438 that is being developed and tested is an EZH2 inhibitor -- it's job is to stop EZH2 from allowing cancer cells to grow willy-nilly.

The presentation at ASH focused on pre-clinical results (stuff they found out in the laboratory) and some phase 1 trial results. As I said, the information about Follicular Lymphoma is pretty limited -- they only report results for one patient, who had stable disease as a result of the treatment. Not an overwhelming endorsement, but enough to move forward.

The pre-clinical results were kind of interesting, too. They combined cells with the inhibitor and CHOP, with good results. Then they tried the individual components of CHOP, and found that just Prednisone helped even more, as did Dexamethasone, another steroid. They also found some activity with BCL2 inhibitors.

It's important to remember that the pre-clinical stuff doesn't involve actual patients; it's just an attempt to narrow down possible options for combinations in later trials.

So what do we have here? A whole bunch of possibilities, and not much else.

Which isn't to say possibilities are bad. It's just really early in the process for this particular treatment.

I'm confident, though, that we'll find something, at some point, that works on EZH2. This particular inhibitor isn't the only one being developed that targets EZH2; the results of research on another possibility were discussed about a year and a half ago in the journal Nature.

I'm also confident that all of this research adds to a bigger picture. Even though EZH2 only effects 22% of us FL patients, our broader understanding of the pathways that lead to cancer can only help researchers as they figure out ways to attack other pathways, as they become known.

So for this research -- right now? Meh. In the future? Lots to hopeful about.

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