A study looking at PARP inhibition in diffuse large B cell lymphoma opens the door to a new way to treat this common type of cancer, according to study author Izidore S. Lossos, M.D., endowed director of the Lymphoma Program at Sylvester Comprehensive Cancer Center and head of the Hematological Malignancies Site Disease Group.
Findings by Dr. Lossos and his team published in Cancer Cell suggest that inhibitors of the enzyme poly ADP ribose polymerase (PARPis) and chemotherapy could work well together to inhibit LMO2-positive diffuse large B cell lymphoma tumor growth.
Diffuse large B cell lymphomas expressing LMO2 protein have deficient homologous recombination DNA repair, and tumors expressing the protein are sensitive to PARPis.
PARP inhibitors are currently used in the treatment of solid tumors. This paper is the first to look at PARP inhibition in diffuse large B cell lymphoma, Dr. Lossos and study co-author Ramiro E. Verdun, Ph.D., demonstrated a new function of LMO2.
“We demonstrated that, while in the cell, LMO2 regulates the choice between error-free and error-prone DNA repair pathways, allowing the introduction of normal B cell mutation,” explained Dr. Lossos.
They went on to discover the potential role for PARPis, which can be used to impair specific DNA repair mechanisms or pathways.
“It was shown that cells in which homologous recombination is inhibited cannot tolerate the presence of PARPi and they die. So, PARPi can induce cell death in cells that express high levels of LMO2,” he said. “We also demonstrated that if you combine PARPi with chemotherapy, you further increase cell death.”
The research suggests a new way to treat diffuse large B cell lymphoma patients. The findings identify a biomarker which can alert providers as to which patients will respond to treatment with a PARP inhibitor. Dr. Lossos and colleagues also generated a specific monoclonal antibody that can be used to identify which patients’ tumors express LMO2.