A Potential New Inhibitor

I saw news recently about a potential new inhibitor. It's so new that I'm not even sure its being tested in Follicular Lymphoma. But it does say some interesting things about clinical trials and treatments anyway.

The news came from a press release with the title "Glenmark receives acceptance from U.S. FDA on its IND application for GRC 54276 to proceed with a Phase 1/2, first-in-human clinical study of the molecule for the treatment of patients with advanced solid tumors and lymphomas." 

A few important things here.

First, the treatment is called GRC 54276, and it is a Hematopoietic Progenitor Kinase 1 (HPK1) inhibitor. As you know if you've been reading for a while, in general, an inhibitor is a treatment that inhibits or stops something from happening. Many cancer begin, or continue, when there is a problem in a chain of events that keeps our bodies running well. So in order for a cell to grow normally, a gene controls an enzyme that signals to a protein that signals to another enzyme that signals to another protein to allow a cell to die. If something happens to that gene, then the whole chain gets thrown off, and the cell doesn't die. And that's what cancer is (to oversimplify) -- a bunch of cells that won't die.

When cancer researchers find one of these chains, they can figure out which part of it is broken. Then they can develop an Inhibitor that inhibits or stops that broken chain of events. In other words, it will tell the body to let the cells die like they're supposed to.  

Hematopoietic Progenitor Kinase 1 (HPK1) inhibitors like this one work by inhibiting a process that keeps T cells from going after cancer cells. As you might know, T cells are immune cells (they are the "T"in "CAR-T"). Inibiting HPK1 will let the T cells do their job and go after the cancer cells.  At least that's the theory right now.

The company that makes the inhibitor has been given permission to begin a phase 1/2 trial in the U.S. They will be able to test the treatment on patients with "advanced solid tumors and lymphomas." So that's why I'm not even sure if this will be a treatment for Follicular Lymphoma. Phase 1 trials are often kind of broad like this, and will test the treatment on patients with several lymphomas (the specific ones aren't mentioned in the press release). Interestingly, the original trial in India involved patients with Hodgkins Lymphoma, not Non-Hodgkins Lymphoma. 

The other interesting thing about this trial is that it involves both lymphomas and solid tumors. We're so used to thinking about cancer in terms of body parts. All breast cancers must be the same, right? Not at all true. More and more, researchers are finding that cancers are about these kinds of genetic processes -- those chains of events. And that same chain of events happens whether the cell is in the blood, or the stomach, or the lung. That's not true for every cancer, but we're probably moving to a place where we don't think of cancer in such local terms.

The final important thing to me is that there is still a lot of great research happening in inhibitors. With the problems that we saw with PI3K inhibitors, it's easy to lump them all together. But there is still lots of excellent research happening in finding those chains of events and figuring out how to inhibit the issues that come with them. Very cool, research.

All of this reminds me that ASCO is coming up soon -- the first week of June. The abstracts should be coming out soon. I'll start sharing once I get access.