Speaker: Dr. Guillermo Velasco Díez, deparment of Biochemistry and Molecular Biology, School of Biology, Complutense University. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040-Madrid. Spain

A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer and specifically of gliomas. In our group we have contributed to clarify the mechanism of cannabinoid anticancer action that relies, at least largely, on the ability of these agents to stimulate autophagy-mediated cancer cell death via upregulation of the pseudokinase TRIB3 and the modification of the sphingolipid profile of autophagosomes. We also found that the combined administration of cannabinoids and temozolomide produces a strong anticancer effect, which correlates with an intense activation of the signalling route that triggers the activation of cytotoxic autophagy. Research conducted in our group has also led to the identification of mechanisms of resistance to cannabinoid anticancer action. For example, up-regulation of the growth factor Midkine (MDK) promotes resistance to cannabinoid anticancer action in gliomas via stimulation of the Anaplastic Lymphoma Kinase tyrosine kinase receptor (ALK). All these preclinical findings have facilitated the promotion of clinical studies to investigate the safety and efficacy of the combined administration of THC+CBD and temozolomide in GBM. In this presentation I will discuss these issues and other possible future studies that may help to clarify whether cannabinoids may be useful as anticancer agents in patients with gliomas or other cancers. Likewise, beyond cannabinoid anticancer action, I will discuss the role of the MDK/ALK axis in glioma that has also led to the development of clinical studies to test the efficacy of ALK inhibitors in GBM.

Host: José Miquel Lizcano, head of group Protein kinases in cancer research (VHIR)