Malignant lymphocytes from a patient with chronic lymphocytic leukemia. Image: Dr. Sina Oppermann.
In a paper recently published in the journal Blood, Dr. David Andrews’ group used high-content screening to test 320 kinase inhibitors and identify ones that, when given in combination with venetoclax, can overcome resistance to the drug. Venetoclax inhibits the anti-apoptotic protein Bcl-2 and received breakthrough status from the U.S. Food and Drug Administration this year. It is available in the U.S. to treat patients with chronic lymphocytic leukemia (CLL). Using cells from patients with CLL, Andrews and Dr. David Spaner, an oncologist at Sunnybrook Health Sciences Centre, found that for approximately half of the CLL patient samples, the kinase inhibitor sunitinib enhanced venetoclax-mediated cell killing dramatically compared to venetoclax alone. This proof-of-principle study demonstrates the feasibility of using high-content screening to individualize treatment regimens for patients and paves the way for a clinical trial examining the safety and efficacy of sunitinib and venetoclax in combination.
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