Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

Abstract

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer

“…A study by Yasmin-Karim et al revealed that a superior pancreatic cancer treatment outcome could be achieved using the combination of cannabinoids and radiotherapy. 7 Similar findings have been demonstrated in a brain glioma cancer model. 67 Improved survival was also demonstrated with IT administration of cannabinoids into subcutaneously implanted murine PANC-02 pancreatic cancers measuring 6 mm in maximum dimension.…”

“…67 Improved survival was also demonstrated with IT administration of cannabinoids into subcutaneously implanted murine PANC-02 pancreatic cancers measuring 6 mm in maximum dimension. 7 Furthermore, treating Kras, P53, and Cre mice with a combination of CBD (100 mg/kg) by daily intraperitoneal (IP) administration and gemcitabine (100 mg/kg) by IP administration every 3 days, IP after 80 days of age prolonged the animal survival three times more than vehicle or gemcitabine treatment alone. 61…”

“…6 There are more than 60 phytocannabinoid entities found in cannabis plant extracts, among which there are currently two of main clinical interest: cannabidiol (CBD) and tetrahydrocannabinol (THC). 7,8 Endocannabinoids are endogenous cannabinoids that include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), involved in a variety of physiological and cognitive processes. Several synthetic cannabinoid compounds have been produced such as the aminoalkyl indole derivative WIN-55 that mimics THC and JWH-133, a potent CB2 receptor agonist that has anti-inflammatory effects.…”

Future Aspects for Cannabinoids in Breast Cancer Therapy

“…AEA inhibits the proliferation of breast cancer cells through nerve growth factor (NGF) and prolactin, by downregulating the NGF receptor and prolactin receptor, respectively [69]. The inhibitory effect of AEA on prolactin receptors may regulate the cancer-directed immune system, as prolactin is a potent endogenous proliferative agent of B and T cells [70]. Furthermore, AEA inhibits cell cycle progression by preventing G1/S transition, as demonstrated in the human prolactin sensitive breast epithelioid EFM-19 cell line [70].…”

“…The inhibitory effect of AEA on prolactin receptors may regulate the cancer-directed immune system, as prolactin is a potent endogenous proliferative agent of B and T cells [70]. Furthermore, AEA inhibits cell cycle progression by preventing G1/S transition, as demonstrated in the human prolactin sensitive breast epithelioid EFM-19 cell line [70]. Similar to AEA, the endocannabinoid 2-AG also exerts antiproliferative activity in MCF-7 and T-47D cells [69], as well as in EMG-19 breast cancer cells [70].…”