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Cannabinoid Signaling in Cancer

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Recent Advances in Cannabinoid Physiology and Pathology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1162))

Abstract

The family of chemical structures that interact with a cannabinoid receptor are broadly termed cannabinoids. Traditionally known for their psychotropic effects and their use as palliative medicine in cancer, cannabinoids are very versatile and are known to interact with several orphan receptors besides cannabinoid receptors (CBR) in the body. Recent studies have shown that several key pathways involved in cell growth, differentiation and, even metabolism and apoptosis crosstalk with cannabinoid signaling. Several of these pathways including AKT, EGFR, and mTOR are known to contribute to tumor development and metastasis, and cannabinoids may reverse their effects, thereby by inducing apoptosis, autophagy and modulating the immune system. In this book chapter, we explore how cannabinoids regulate diverse signaling mechanisms in cancer and immune cells within the tumor microenvironment and whether they impart a therapeutic effect. We also provide some important insight into the role of cannabinoids in cellular and whole body metabolism in the context of tumor inhibition. Finally, we highlight recent and ongoing clinical trials that include cannabinoids as a therapeutic strategy and several combinational approaches towards novel therapeutic opportunities in several invasive cancer conditions.

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Abbreviations

2-AG:

2-arachindonoylglycerol

AEA:

anandamide

AMPK:

5′ AMP-activated protein kinase

CBD:

cannabinoids

CBR:

cannabinoid receptor

COX-2:

cyclooxygenase-2

CXCL:

C-X-C motif chemokine ligand

EGFR:

epidermal growth factor receptor

EMT:

epithelial to mesenchymal transition

E:R:

endoplasmic reticulum

mTOR:

mammalian target of rapamycin

PPAR:

peroxisome proliferator-activated receptors

ROS:

reactive oxygen species

TAMs:

tumor associated macrophages

THC:

Δ9-tetrahydrocannabinol

TME:

tumor microenvironment

TRPV2:

transient receptor potential cation channel subfamily V member 2.

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Acknowledgements

This work is supported in part by the Department of Defense Level II Breakthrough Award and Pelotonia IDEA Award.

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Author notes

  1. The authors Subhadip Das and Kirti Kaul have equally contributed to this chapter.

Authors and Affiliations

  1. Department of Pathology, The Ohio State University, Columbus, OH, USA

    Subhadip Das, Kirti Kaul, Sanjay Mishra, Manish Charan & Ramesh K. Ganju

  2. Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    Subhadip Das, Kirti Kaul, Sanjay Mishra, Manish Charan & Ramesh K. Ganju

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  1. Subhadip Das
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Correspondence to Ramesh K. Ganju .

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  1. Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya

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Das, S., Kaul, K., Mishra, S., Charan, M., Ganju, R.K. (2019). Cannabinoid Signaling in Cancer. In: Bukiya, A. (eds) Recent Advances in Cannabinoid Physiology and Pathology. Advances in Experimental Medicine and Biology, vol 1162. Springer, Cham. https://doi.org/10.1007/978-3-030-21737-2_4

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