Breaking Down Resistance to BTK Inhibitors

Skye Montoya, a PhD candidate at the University of Miami Sylvester Cancer Center, discusses new research into the novel bioavailable degrader of Bruton tyrosine kinase (BTK), NX-2127.

This is a new mechanism of treatment for patients with chronic lymphocytic leukemia or B-cell malignancies that looks to degrade the BTK protein altogether instead of just inhibiting it. The novel degrader NX-2127 has already shown promising early signs of degrading BTK, and impacting mutations of the BTK protein, such as BTK-wild type.

By catalyzing the degradation of the BTK protein this becomes an important target for treatment of patients with B-cell malignancies as the B-cell development, differentiation, and signaling helps lymphoma and leukemia cells survive.

Now, research that Montoya is a part of, is looking at finding the signaling mechanism in the disease and how the degrader can be carried downstream to degrade all of the protein. She discusses how this is the first BTK degrader to actively be used with patients in the clinic showing promising activity for these patients. Moreover, she discusses how this impacts patients who have had to undergo multiple lines of therapy.

TRANSCRIPTION:

0:08 | We have a lot of different inhibitors for BTK, especially with treatment for CLL or other [patients with] B-cell malignancies. But when resistance occurs from acquired mutations to BTK, it becomes a problem of finding a way to treat the patients. These degraders, especially our new BTK degrader NX-2127, offers a very exciting avenue, as far as, how we can treat patients that did develop resistance, and especially for the patients that have been on multiple lines of therapy in the past.