Tamara Lah Turnsek

National Institute of Biology, Slovenia

Title: Brain Tumor Glioblastoma Progression and Possible Adjuvant Treatment with Repurposed and Natural Compounds

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Biography

Prof. Dr. Tamara Lah Turnšek obtained her PhD in 1981 at University of Ljubljana and Josef Stefan Institute (IJS) with a Thesis in the field of protein biochemistry. She has been employed at IJS as a researcher for about 20 years, with several intermediate periods of visiting foreign institutions, first already as PhD candidate in Newcastle upon Tyne, UL, Assistant Professor at the Faculty of Medicine at Wayne State University in Detroit and later as Visiting Professor and Director of Metastasis Research at Albert Einstein Medical Centre in Philadelphia, PA. Soon after her postdoctoral studies, she committed her research to cancer, which she performed initially at IJS and later at National Institute of Biology (NIB). She became the Director of NIB in 1995-2018 and established the Department of Genetic Toxicology and Cancer Biology, where she continues to work to this day, remaining the Leader of its research programme and consultant to the current Director.

Abstract

Plant cannabinoids (CBN)  are multi targeting phenolic terpenoids, isolated from the active components of Cannabis sativa that have been used in medicine for thousands of years to ameliorate various health symptoms. Over past 50 years cannabinoids have been witnessing a renaissance of research and clinical application as antitumor drugs. Compounds of similar structures are also produced in higher organism, including humans, and termed endocannabinoids. Their effects are exerted either via cell type specific cannabinoid receptors (CB1) an CB2 and/or less specific G-protein binding receptors (GPR) and ionotropic receptors (TRPV) that are triggering various cross-signaling cellular pathways, targeting and resulting in responses of pathophysiological processes. Three major components, the  Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and cannabigerol (CBG), recently recognized as anticancer drugs,  have selective effects on cancer cells and experimental animals, as well as on patients tumors’ growth and invasion and other disease-associated process. These are being used in palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC, the only psychoactive substance is also used for anorexia and weight loss.

Glioblastoma are the most frequent, aggressive, and in most fatal among brain and other, cancer general. Early relapses are unavoidable despite standard-of-care treatment, causing death in about 1.5 month after diagnosis. However, the known psychoactive effects of THC hamper its medical applications in glioblastoma patients with potential cognitive impairment, due to the progression of the disease. Therefore, in our recent  studies we were the first to replace THC with nontoxic CBG,

and demonstrated that CBG had comparable killing effects to THC, and that  its combination with CBD inhibited the invasion of glioblastoma cells, including  chemotherapy therapy-resistant glioblastoma stem cells, which are the root of cancer development (Lah et al., 2021)  CBG thus presents a new, yet unexplored adjuvant treatment strategy of glioblastoma treatment.

Glioblastoma are also highly heterogenous tumors with respect to the variability in cancer and stromal cells comprising the tumors. Therefore not all patients respond the same way to the same concentration  and combination of the CBNs. In our studies we aimed to explore how the genetic fingerprint of individual patients’  tumors would predict the outcome of cannabinoid treatment. We hypotheses, that the relative levels of  CBN receptors CB1, CB2, TRPV1, TRPV1 and GPR55 would predict the intensity of  various CBNs and their combinations response in the in vitro primary glioblastoma cells cultures. In this lecture we will present the platform set up in vitro, using patients-derived tumor cells, grown in 2D and 3 D spheroid cultures, to test the effect of cannabinoids. In further studies also combinations with standard therapeutic, such as temozolomide and irradiation are tested. We thus aim to translate in vitro observation to in vivo  application of cannabinoids as antitumor drugs,

In conclusion, we have demonstrated that THC has little added value in combined CBN treatment og gllioblastoma, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role, not only in palliative care of brain tumor patients, but also to inhibit fast glioblastoma growth and intracranial spread.