"Despite enormous advances in therapies for chronic lymphocytic leukemia (CLL) that target the B-cell receptor (BCR) signaling pathway, there is still room for improvement, according to investigators at the Mayo Clinic.
Bruton’s tyrosine kinase (BTK) and phosphoinositide-3 kinase delta (PI3Kδ) inhibitors are major players in mediating BCR signaling, yet both have off-target effects.
“These agents are not curative, and resistance develops,” explained Neil Kay, MD, of the Mayo Clinic in Rochester, Minnesota.
He described the Axl receptor tyrosine kinase and its inhibitor, TP-0903, at Lymphoma & Myeloma 2015, and discussed how it may be another promising target for CLL therapy.
The team found that, by inhibiting Axl with TP-0903, they were able to induce robust apoptosis in CLL B cells, including those from high-risk 17p– and 11q– CLL.
He said Axl inhibition is a therapeutic opportunity in that these inhibitors are orally bioavailable and would be candidates for clinical testing. These inhibitors may minimize drug resistance and prevent the emergence of Richter’s transformation, he added."
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Photo: Making like a tree branch stump - the Tawny Frogmouth owl. I wouldn't have even noticed this tree branch in disguise if he hadn't flown off as I walked within a few metres of him...