Tuesday, January 6, 2015

Mocetinostat for Follicular Lymphoma

A new phase 2 clinical trial is just starting at Sloan Kettering in New York, investigating the effectiveness of Mocetinostat in patients with DLBCL and, more importantly for us, Follicular Lymphoma.

Mocetinostat is a benzamide histone deacetylase inhibitor. That's probably going to require a little explanation.

If you've been following developments in cancer treatments, the  you know more and more of them are "inhibitors." That is, instead of trying to kill off the cancer cells the way traditional chemotherapy does, inhibitors try to stop (or inhibit) the processes that cancer cells need to live.

For Mocetinostat, that means inhibiting the process that involves the benzamide histone deacetylase. Histones are proteins that help cells structure DNA, so when the cell tries to copy itself, the new copy will be like the old cell. When the histone is messed with (which is what Mocetinostat does), the cancer cell can't make a copy of itself.

It's a little more complicated than that, but you get the basics.

Now, what makes this Mocetinostat trial special is that it relies on genetic profiling, something that has been promised for a while. In other words, we are at a point where we can examine each individual patient's genetics. We know that not all Follicular Lymphomas are the same -- even though they look the same under a microscope, if we look closer we can see that not everyone's FL was caused in the same way. If we can figure out which gene mess-ups caused each patient's cancer, and we can target those mess-ups, then we have a better chance at successfully treating each patient.

And that's just what's happening with this trial. Researchers know that Mocetinostat works best on patients that have mess-ups on two particular genes, known as CREBBP and EP300. These mess-ups happen to be common to DLBCL and Follicular Lymphoma. So patients in the trial first had a genetic profile done to make sure they had those two particular genes affected, and thus have a better chance of the treatment working.

A total of 54 patients will be enrolled. Half of them will be Follicular Lymphoma patients.

This strikes me as pretty typical of what we can expect in the future -- treatments that not only target particular pathways, but that target particular patients. That's the kind of "personalized medicine" that we've been hearing about for a few years now.


Anonymous said...

Hi have you heard of double hit lymphoma? One of NZ famous cricketers follicular lymphoma has transformed into this. I had never come across it and I thought I was quite well informed. Guess not

Lymphomaniac said...

Hi Mel.
Yes, I've heard of double-hit. It's sometimes considered a "new" lymphoma, but I think the disease isn't new, it just seems that way because we have better tools to detect it (since it involves two different gene mutations). It's a tough one to treat because of that. On the other hand, knowing that there are particular genetic mutations might make it easier to find a targeted treatment down the road.
I hope your cricketer does, and gets to see some of the Cup.

Anonymous said...

I hope so too. He has chosen not to have chemo, it was going to be 100 days of chemo which is a long time.