New cancer drug candidates, used in combination, may benefit patients with ‘double-hit’ diffuse large B-cell lymphoma, a rare and treatment-resistant condition. The finding was in a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, held April 16-20 in New Orleans.
Researchers at the Roswell Park Cancer Institute in New York, led by Francisco Hernandez-Ilizaliturri, clinical chief of the institute’s Lymphoma/Myeloma Service, reviewed a database of 650 patients with diffuse B-cell lymphoma — the most common type of non-Hodgkin lymphoma — to identify 36 people with the rare circumstance of carrying two or more disease-causing mutations in the genes c-MYC, BCL2 and BCL6.
The rare condition, known as ‘double-hit’ diffuse large B-cell lymphoma, is notoriously difficult to treat with standard chemotherapy. New treatments targeting these proteins are under development.
In the study, “Investigating novel targeted therapies for double hit diffuse large B-cell lymphoma (DH-DLBCL),” the team tested three drug candidates, known as ABT-199, JQ-1, and carfilzomib, in preclinial studies and noted that they induced cancer cell death. The effects were observed to increase with both dose and time.
Using cultured cancer cells treated with the drugs, the team observed synergistic effects when ABT-199 was applied in combination with carfilzomib. Synergy was also noted also when ABT-199 was combined JQ-1, although to a lesser extent.
“Increasing knowledge of genetics and molecular pathways has helped us identify a subgroup of patients who harbor aggressive aberrant gene mutations. Understanding the mechanisms of action and clarifying how these potential therapies work to inhibit cancer cell growth may result in improved outcomes for patients diagnosed with this aggressive type of lymphoma,” Dr. Hernandez-Ilizaliturri, the study’s senior author, said in a press release.
“As we continue to gain more insight into the finer aspects of cancer biology by understanding the molecular pathways through which the cancer cells grow, we can identify strategies to effectively exploit the growth mechanism of these tumors and hopefully translate that knowledge into improved cure rates for our patients,” added Dr. Priyank Patel, study first author and a fellow in the Department of Medicine at Roswell Park.