Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 14:11:821785.
doi: 10.3389/fonc.2021.821785. eCollection 2021.

Direct Cytotoxic and Indirect, Immune-Mediated Effects of Local Anesthetics Against Cancer

Alejandra Wu Chuang  1   2 , Oliver Kepp  1   2 , Guido Kroemer  1   2   3 , Lucillia Bezu  1   2   4
Affiliations
Review

Direct Cytotoxic and Indirect, Immune-Mediated Effects of Local Anesthetics Against Cancer

Alejandra Wu Chuang et al. Front Oncol. .

Abstract

Local anesthetics are frequently employed during surgery in order to control peri- and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.

Keywords: cancer; cell death; immunity; local anesthetics; surgery.

PubMed Disclaimer

Conflict of interest statement

OK is scientific co-founder of Samsara Therapeutics; GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Samsara, Sanofi, Sotio, Vascage and Vasculox/Tioma. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Samsara Therapeutics and Therafast Bio. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

Figures

Figure 1
Figure 1
Direct cytotoxic effects of local anesthetics. Scheme summarizing direct effects of local anesthetics on cancer cells including the regulation of signaling pathways that control proliferation, survival and migration of cancer cells. Ca2+, calcium ion; CHOP, C/EBP Homologous protein; Cyt, Cytoplasm; DNMT, DNA methyltransferase; EGFR, epidermal growth factor receptor; ER, endoplasmic reticulum; Ext, extracellular space; IGFR, insulin growth factor receptor; Mg2+, magnesium ion; Na+, sodium ion; TNFR, tumor necrosis factor receptor; ROS, reactive oxygen species; PERK, protein kinase R-like ER kinase.
Figure 2
Figure 2
Indirect effects of local anesthetics Schematic representation of indirect effects induced by local anesthetics on cancer cells and immune effectors: inhibition of inflammation, inhibition of cancer cell proliferation and migration, surgical stress control, reduction of neoangiogenesis, preservation of immunity and clinical effects. IFN, interferon; IL, interleukin; MMP, matrix metalloproteinase; NK, natural killer cell; VEGF, vascular endothelial growth factor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J EM, Lam F, Colombet M, Mery L, Pineros M, et al. . Global Cancer Observatory: Cancer Today (2020). Lyon: International Agency for Research on Cancer. Available at: https://gco.iarc.fr/today (Accessed February 2021). 2020.
    1. Sullivan R, Alatise OI, Anderson BO, Audisio R, Autier P, Aggarwal A, et al. . Global Cancer Surgery: Delivering Safe, Affordable, and Timely Cancer Surgery. Lancet Oncol (2015) 16(11):1193–224. doi: 10.1016/S1470-2045(15)00223-5 - DOI - PubMed
    1. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging Biological Principles of Metastasis. Cell (2017) 168(4):670–91. doi: 10.1016/j.cell.2016.11.037 - DOI - PMC - PubMed
    1. Yang H, Xia L, Chen J, Zhang S, Martin V, Li Q, et al. . Stress-Glucocorticoid-TSC22D3 Axis Compromises Therapy-Induced Antitumor Immunity. Nat Med (2019) 25(9):1428–41. doi: 10.1038/s41591-019-0566-4 - DOI - PubMed
    1. Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, et al. . Increased Surgical Stress Promotes Tumor Metastasis. Surgery (2003) 133(5):547–55. doi: 10.1067/msy.2003.141 - DOI - PubMed

LinkOut - more resources