New therapies for treating non-Hodgkin’s lymphomas (NHL) are joining tried and tested therapies, but there needs to be an understanding of how rational combinations match within the “hallmarks of cancer,” according to a recent review article in the Journal of Clinical Oncology by Arizona Cancer Center physician-scientist Daruka Mahadevan, MD, PhD, director of the center’s Phase I New Drug Development Program.
Dr. Mahadevan, a member of the AZCC’s Lymphoma Research Consortium and principal investigator of Project 1 of the Lymphoma SPORE, says finding the right combination of drugs to treat relapsed and refractory NHL is like putting together a puzzle, a task that is challenging and a moving target.
In the article, Dr. Mahadevan and co-author Richard I. Fisher, MD, of the University of Rochester, chairman of the Lymphoma committee of SWOG and principal investigator on the Lymphoma SPORE with Thomas P. Miller, MD, compile the results of about two dozen early phase clinical trials involving more than 750 B-NHL and T-NHL patients and discuss these studies within the context of overlapping oncogenic pathways.
The original hallmarks of cancer were six physiologic traits introduced in 2000 by cancer researchers Robert A. Weinberg, PhD, and Douglas Hanahan, PhD, but these have been extended to 10 hallmarks proposed by Dr. Mahadevan (WebMD, 2010) and the former authors in 2011 (Cell). Lymphoma researchers have focused on diagnostic-prognostic markers from large cohorts of patients but have for the most part avoided “druggable” targets, that is, targets within the lymphoma cells for which drugs can be discovered and designed to kill these cells.
Dr. Mahadevan said a "therapeutic signature" can be developed for each of the major subtypes of NHL using the 10 hallmarks of cancer, to generate hypothesis driven combination therapies that may be incorporated into novel biomarker-driven early phase clinical development programs.
“We are all digging deeper to find the drug targets and combination therapies that would lead to meaningful responses and cures for our patients” he said.