Inflammation in the tumor0020microenvironment is now widely acknowledged as a hallmark of cancer (Hanahan, 2022). The tumor microenvironment is rich in both de novo synthetized and dietary fatty acids (FAs), including those derived from the oxidation of arachidonic acid and other polyunsaturated FAs known as eicosanoids.
Pro-inflammatory eicosanoids (including prostanoids and leukotrienes), which are produced by both tumor cells and stroma, can impact tumor progression through various mechanisms (Wang and Dubois, 2010). These biologically active lipids can influence tumor cell proliferation, apoptosis, migration, and invasion. They can also affect tumor neo-angiogenesis and alter tumor antigenicity, ultimately shaping the tumor microenvironment. Eicosanoids play a crucial role in the complex interplay between tumor cells, stroma, inflammatory cells, and platelets, opening new avenues of research for understanding the relationship between different pathophysiological mechanisms.
The eicosanoids in cancer, volume II, Research Topic combines: 1) a review presenting the current understanding of the role of FAs in colorectal cancer progression (Hoxha and Zappacosta); 2) a meta-analysis of randomized clinical trials on the efficacy of omega-3 polyunsaturated FAs in colorectal cancer (Liu et al.); 3) two articles presenting cyclooxygenase (COX)-2 dependent and independent approaches to improve the sensitivity to chemotherapy (Lin et al.) or to reduce inflammation and oxidative stress (Apweiler et al.).
A comprehensive review by Hoxha and Zappacosta focuses on the involvement of FAs and their metabolites in colorectal cancer. Data presented in the review indicates that FAs may contribute to the development and progression of colorectal cancer through several mechanisms. The authors, therefore, suggest that enzymes involved in FA metabolism could represent novel therapeutic targets for adjuvant therapy in cancer patients.
A meta-analysis by Liu et al. systematically evaluated the efficacy of omega-3 polyunsaturated FAs on several clinical parameters associated with colorectal cancer progression. The meta-analysis reveals that omega-3 supplementation reduces the level of some inflammatory cytokines and shortens the length of hospitalization but does not affect the outcome of postoperative colorectal cancer patients.
COX-2 is often implicated in the chemoresistance of certain malignant tumors, and its inhibition with nonsteroidal anti-inflammatory drugs (NSAIDs) may enhance the sensitivity of tumors to anticancer drugs (Bell et al., 2022). Lin et al. report a novel molecular mechanism of COX-2 upregulation in chemoresistant non-small cell lung cancer (NSCLC) cells. The authors show that a reactive oxygen species-ERK1/2-NF-κB signaling axis and prostaglandin (PG)E2-PGE2 receptors-ERK1/2 positive feedback loop are involved in the COX-2 upregulation by cisplatin, which induces multidrug resistance of NSCLC cells through upregulation of BCL2 expression and the subsequent attenuation of cell apoptosis. COX-2 inhibition with the NSAID celecoxib reverses the chemoresistance of NSCLC cells in vitro and in vivo.
Apweiler et al. report that another NSAID, acetaminophen, and its metabolite, AM404, can reduce interleukin-1β-induced PGE2 generation through a COX-independent pathway that appears linked to reductions in oxidative stress in SK-N-SH neuroblastoma cells.
Our knowledge of the relationship between FAs and cancer is incomplete. It is necessary to research further the various types of FAs and their metabolites to understand their clinical significance in cancer diagnosis and treatment. While we have more information on the impact of COX-2 and its metabolites on cancer initiation, progression, metastasis, and resistance, the use of NSAIDs combined with chemotherapy or immunotherapy has not been well established yet.
Statements
Author contributions
PP, ES, and ER wrote the manuscript. All authors contributed to the article and approved the submitted version.
Conflict of interest
The 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.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1
Bell C. R. Pelly V. S. Moeini A. Chiang S. C. Flanagan E. Bromley C. P. et al (2022). Chemotherapy-induced COX-2 upregulation by cancer cells defines their inflammatory properties and limits the efficacy of chemoimmunotherapy combinations. Nat. Commun.13 (1), 2063. 10.1038/s41467-022-29606-9
2
Hanahan D. (2022). Hallmarks of cancer: New dimensions. Cancer Discov.12 (1), 31–46. 10.1158/2159-8290.CD-21-1059
3
Wang D. DuBois R. (2010). Eicosanoids and cancer. Nat. Rev. Cancer10 (3), 181–193. 10.1038/nrc2809
Summary
Keywords
eicosanoids, cancer, arachidonic acid, oxylipins, inflammation
Citation
Patrignani P, Smyth EM and Ricciotti E (2023) Editorial: Eicosanoids in cancer, Volume II. Front. Pharmacol. 14:1224623. doi: 10.3389/fphar.2023.1224623
Received
17 May 2023
Accepted
06 June 2023
Published
14 June 2023
Volume
14 - 2023
Edited and reviewed by
Dieter Steinhilber, Goethe University Frankfurt, Germany
Updates
Copyright
© 2023 Patrignani, Smyth and Ricciotti.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Paola Patrignani, ppatrignani@unich.it; Emanuela Ricciotti, emanuela@pennmedicine.upenn.edu
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.