January 2020
Chiara Laezza, Cristina Pagano, Giovanna Navarra, Olga Pastorino, Maria Chiara Proto, Donatella Fiore, Chiara Piscopo, Patrizia Gazzerro, and Maurizio Bifulco
Abstract
In recent years, the endocannabinoid system has received great interest as a potential therapeutic target in numerous pathological conditions. Cannabinoids have shown an anticancer potential by modulating several pathways involved in cell growth, differentiation, migration, and angiogenesis. However, the therapeutic efficacy of cannabinoids is limited to the treatment of chemotherapy-induced symptoms or cancer pain, but their use as anticancer drugs in chemotherapeutic protocols requires further investigation. In this paper, we reviewed the role of cannabinoids in the modulation of signaling mechanisms implicated in tumor progression.
Conclusions
The literature strongly suggests a role for the ECS in the pathogenesis of cancer. It is evident that cannabinoids target key signaling pathways affecting all the hallmarks of cancer. However, they complement the conventional chemotherapeutic regimens currently used preventing pain, nausea, and vomiting. Further studies will be necessary to fully elucidate their clinical relevance for cancer treatment.
More intensive basic research will allow us to better understand the intracellular signaling pathways in cannabinoid anticancer action, identify intracellular factors modulated by cannabinoids, and discern tumors sensitive or resistant to cannabinoids.
Results from these studies are essential to clarify whether cannabinoids could be helpful in cancer treatment. An interesting idea is their synergistic interaction with some conventional cytostatic drugs as well as their capacity to suppress metastasis and angiogenesis.
Indeed, several studies described that Δ9-THC and CBD increased the cytostatic effects of chemotherapeutic drugs, such as the combination of CBD with DOX in vivo mouse model of triple-negative breast cancer (TNBC) that showed significantly higher activity than DOX alone and no obvious signs of toxicity were observed in mice treated with combination treatment. More, the promising data from studies on animal models of glioblastoma treated with Δ9-THC and temozolomide have led to clinical trials using combinatorial treatments of nabiximols and temozolomide in patients with recurrent glioblastoma.
Taken together, cannabinoids and compounds modulating the endocannabinoid system may enrich the range of used chemotherapeutic agents as a pharmacotherapeutic option for cancer treatment. In the coming years, the discoveries on the endocannabinoid system may allow the development of more efficacious and safer compounds. Moreover, observations obtained from next-generation sequencing of tumors can best identify potent combinations of cannabinoids formulations and tumors with specific characteristics.
These new approaches could lead to the identification of cannabinoid therapy-associated biomarkers in tumor biopsies or, ideally, high levels of resistance factors released by cancer cells. These biomarkers would conceivably relate to the expression and activity of cannabinoid receptors and then define the sensitivity of a particular tumor to cannabinoid-based therapies.
Future studies should also emphasize investigations of administration routes, delivery schedules, and absorption of medicinal cannabis to further explore its application in cancer management, allowing a better assessment of the efficacy of cannabinoids in the fight of cancer.
