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Review
. 2024 Apr 30;22(1):402.
doi: 10.1186/s12967-024-05205-8.

Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis

Neda Dadgar  1 , Christopher Sherry  2 , Jenna Zimmerman  2 , Hyun Park  2 , Catherine Lewis  2 , Albert Donnenberg  2 , Ali H Zaidi  2 , Yong Fan  2 , Kunhong Xiao  3 , David Bartlett  2 , Vera Donnenberg  4 , Patrick L Wagner  5
Affiliations
Review

Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis

Neda Dadgar et al. J Transl Med. .

Abstract

Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.

Keywords: IL-6; Peritoneal carcinomatosis; Targeted therapy; Tumor immune microenvironment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Overview of interleukin-6 (IL-6) impact on key hallmarks of cancer. IL-6 drives sustained proliferative signaling, activation of invasion and metastasis, and contributes to genome instability and immune evasion within the tumor microenvironment. Additionally, IL-6 enables replicative immortality, promotes angiogenesis, exerts anti-apoptotic effects, and influences cellular energetics, collectively driving cancer progression and highlighting its pivotal role in tumor biology. Created with BioRender.com
Fig. 2
Fig. 2
Illustrated here is the crucial role of IL-6 in driving peritoneal carcinomatosis (PC) progression. It shows IL-6’s involvement in tumor proliferation, adhesion, epithelial-mesenchymal transition (EMT), and other oncogenic pathways. The figure spotlights the IL-6/STAT3 signaling pathway’s redundancy and its systemic effects, emphasizing molecular alterations that lead to PC’s aggressive nature. “Created with BioRender.com.”
See this image and copyright information in PMC

References

    1. Tepel J, Ajah D. The natural course of peritoneal carcinomatosis (PC). Peritoneal tumors and metastases: Surgical, intraperitoneal and systemic therapy. Springer; 2021. pp. 55–8.
    1. Kepenekian V, Bhatt A, Péron J, Alyami M, Benzerdjeb N, Bakrin N, et al. Advances in the management of peritoneal malignancies. Nat Reviews Clin Oncol. 2022;19(11):698–718. doi: 10.1038/s41571-022-00675-5. - DOI - PubMed
    1. Park SJ, Lee EJ, Lee HS, Kim J, Park S, Ham J, et al. Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum. Drug Delivery. 2021;28(1):1179–87. doi: 10.1080/10717544.2021.1937382. - DOI - PMC - PubMed
    1. Sugarbaker PH. Intraperitoneal delivery of chemotherapeutic agents for the treatment of peritoneal metastases: current challenges and how to overcome them. Expert Opin Drug Deliv. 2019;16(12):1393–401. doi: 10.1080/17425247.2019.1693997. - DOI - PubMed
    1. Sun BJ, Lee B. Review of regional therapies for gastric cancer with peritoneal metastases. Cancers. 2022;14(3):570. doi: 10.3390/cancers14030570. - DOI - PMC - PubMed

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