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Endocannabinoids pp 449–472Cite as

Endocannabinoids and Cancer

  • Chapter

Part of the Handbook of Experimental Pharmacology book series (HEP,volume 231)

Abstract

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. They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and cell proliferation in different types of tumours in laboratory animals. By contrast, little is known about the biological role of the endocannabinoid system in cancer physio-pathology, and several studies suggest that it may be over-activated in cancer. In this review, we discuss our current understanding of cannabinoids as antitumour agents, focusing on recent advances in the molecular mechanisms of action, including resistance mechanisms and opportunities for combination therapy approaches.

Keywords

  • Angiogenesis
  • Apoptosis
  • Autophagy
  • Cancer
  • Cannabinoid
  • Cell proliferation
  • Cell signalling
  • Combinational therapy

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Abbreviations

2-AG:

2-Arachidonoylglycerol

ALK:

Anaplastic lymphoma kinase

ATF-4:

Activating transcription factor 4

CB1 :

Cannabinoid CB1 receptor

CB2 :

Cannabinoid CB2 receptor

CBD:

Cannabidiol

CHOP:

C/EBP homologous protein

EGFR:

Epidermal growth factor receptor

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

MDK:

Midkine

mTORC1:

Mammalian target of rapamycin complex 1

mTORC2:

Mammalian target of rapamycin complex 2

THC:

Δ9-tetrahydrocannabinol

TRIB3:

Tribbles-homologue 3

TRPV1:

Transient receptor potential cation channel subfamily V member 1

VEGF:

Vascular endothelial growth factor

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Acknowledgements

Research in the groups of the authors is supported by grants from Spanish Ministry of Economy and Competitiveness (MINECO) (PI12/02248, FR2009-0052 and IT2009-0053 to GV; and PI11/00295 to CS), Comunidad de Madrid (S2011/BMD-2308 to MG), GW Pharmaceuticals (to GV, CS and MG); Fundación Mutua Madrileña (AP101042012 to GV) and Fundació Telemarató (20134031 to GV)

Potential Conflict of Interest

We declare that GW Pharmaceuticals funded part of the research of our laboratory. Likewise, part of the data obtained by the authors in relation with the antitumour action of cannabinoids is included in three patent applications presented by GW Pharmaceuticals.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain

    Guillermo Velasco, Cristina Sánchez & Manuel Guzmán

  2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

    Guillermo Velasco & Manuel Guzmán

  3. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

    Guillermo Velasco

  4. Instituto Universitario de Investigación Neuroquímica (IUIN), Madrid, Spain

    Guillermo Velasco, Cristina Sánchez & Manuel Guzmán

  5. Instituto de Investigación Hospital 12 de Octubre (i + 12), Madrid, Spain

    Cristina Sánchez

  6. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

    Manuel Guzmán

Authors
  1. Guillermo Velasco
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  2. Cristina Sánchez
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  3. Manuel Guzmán
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Corresponding author

Correspondence to Guillermo Velasco .

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Editors and Affiliations

  1. Professor of Neuropharmacology, University of Aberdeen Institute of Medical Sciences, Aberdeen, United Kingdom

    Roger G. Pertwee

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Velasco, G., Sánchez, C., Guzmán, M. (2015). Endocannabinoids and Cancer. In: Pertwee, R. (eds) Endocannabinoids. Handbook of Experimental Pharmacology, vol 231. Springer, Cham. https://doi.org/10.1007/978-3-319-20825-1_16

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