ICRF Grant Explores Cannabinoids’ Antitumoural Effects
Professor David Meiri, a new ICRF Project Grant recipient, talks about his research on a distinct combination of cannabinoids, which are able to induce cell death in leukemia cells.
As a new ICRF grantee, can you briefly describe your research relating to the cannabis plant and its effects on tumors?
Recently, the therapeutic potential of cannabinoids and the unique active compounds of the cannabis plant, have become relevant in cancer research. Cannabis is currently being used by cancer patients, primarily in palliative care, but recent pre-clinical and clinical data suggest that the right plant components can actually exert antitumoral effects.
As cannabinoids have also been shown to play key roles in modulation of the immune system, we tested the effect of cannabis in T-cell acute lymphoblastic leukemia (T-ALL). We found a specific cannabis extract that selectively induces apoptosis (cell death) in T-ALL cells that have a mutation in the signaling receptor Notch1. In humans, more than 50 percent of T-ALL cases display Notch1 autoactivation, making this signaling pathway a strong candidate for new therapeutics. However, thus far, efforts to develop such agents have remained unsuccessful. In our research, we succeeded to isolate three unique cannabinoids that synergistically replicate the effect of the whole extract, resulting in reduced abnormal Notch1 signaling and diminished cancer propagation and burden. With these cannabinoids, we plan to establish a new targeted therapy for the treatment of Notch-dependent cancers such as T-ALL and chronic lymphocytic leukemia (CLL).
Which kinds of cancers are you specifically targeting?
We are currently focusing on T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL), but as aberrant Notch signaling is implicated in various cancer types, including skin, lung, breast, ovarian, cervical, prostate, pancreas, colon, brain and blood tumors, our findings are potentially relevant for combating numerous cancers.
How will ICRF help you to achieve this goal?
With support from ICRF, we hope to reveal cannabinoids’ full mechanism of action, optimize their efficacy and safety, and investigate their effect on Notch1-mutated leukemia cells from human patients.
Dr. Meiri’s laboratory investigates the vast therapeutic potential of naturally-occurring cannabinoids and other bioactive components in various cannabis species. He received his BSc and MSc degrees from Tel Aviv University, where he obtained a PhD in Plant Sciences before turning his focus to cancer research as postdoctoral fellow in the University Health Care Network, Canada. He is currently an Assistant Professor of Biology at the Technion.
About the Research:
Cannabis is already being used by cancer patients, primarily as palliative care to alleviate pain and stimulate appetite while preventing nausea and vomiting. Recently, phytocannabinoids, the unique active compounds of the cannabis plant, have been shown to have therapeutic potential, and accumulating pre-clinal and clinical data suggest the right plant components can actually exert antitumoral effects on specific tumors.
The goal of this project is to identify phytocannabinoids active against T-cell acute lymphoblastic leukemia (T-ALL). Dr. Meiri’s team has recently identified a specific cannabis extract that kills T cell leukemia cells in which mutation of the Notch1 oncogene promotes cell proliferation, as occurs in more than half of all cases of adult T-AL. Building on those results, they have isolated three unique phytocannabinoid compounds that, when co-administered, synergistically replicate this effect. They now proposed to optimize therapy of T-ALL with these combined phytocannabinoids, by examining the efficacy and safety of treatment. They will also learn how these compounds affect the Notch signaling pathway, which is dysregulated in a number of cancer types, in experiments that will pave the way for the establishment of a new drug therapy for the treatment of Notch-dependent cancers.