Inflammation is a key target in cancer treatment because it plays a significant role in cancer development, progression, and resistance to treatment. By targeting inflammatory pathways, therapies can aim to either suppress cancer development, enhance the effectiveness of other treatments, or even trigger an anti-tumor immune response. The neural inflammatory reflex, particularly involving the vagus nerve, is being explored as a potential therapeutic target in cancer treatment. This is because the nervous system plays a complex role in cancer, influencing both tumor growth and the body's response to therapy, including immunotherapy. By modulating the inflammatory reflex, researchers aim to either enhance anti-tumor immune responses or reduce the negative effects of cancer and its treatment. Targeting inflammation as cancer therapy Manni Wang, Siyuan Chen, Xuemei He, Yong Yuan, Xiawei Wei J Hematol Oncol. 2024 Mar 22;17(1):13. Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators in cancer including inflammatory cells, inflammatory cytokines, and their downstream intracellular pathways. In addition, we especially address the role of inflammation in cancer development and highlight the action mechanisms of inflammation-targeted therapies in antitumor response. Finally, we summarize the results from both preclinical and clinical studies up to date to illustrate the translation potential of inflammation-targeted therapies. Inflammation in cancer: therapeutic opportunities from new insights Yifei Xie, Fangfang Liu, Yunfei Wu, Yuer Zhu, Yanan Jiang, Qiong Wu, Zigang Dong, Kangdong Liu Mol Cancer. 2025 Feb 24;24(1):51. As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed. Vagus nerve stimulation: Novel concept for the treatment of glioblastoma and solid cancers by cytokine (interleukin-6) reduction, attenuating the SASP, enhancing tumor immunity Steven Brem Brain Behav Immun Health. 2024 Sep 17;42:100859 Immuno-oncology, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer care with dramatic, long-term responses and increased survival, including patients with metastatic cancer to the brain. Glioblastomas, and other primary brain tumors, are refractory to ICIs as monotherapy or in combination with standard therapy. The tumor microenvironment (TME) poses multiple biological hurdles: blood-brain barrier, immune suppression, heterogeneity, and tumor infiltration. Genomic analysis of the senescence-associated secretory phenotype (SASP) and preclinical models of glioma suggest that an exciting approach would entail reprogramming of the glioma microenvironment, attenuating the pro-inflammatory, pro-tumorigenic cytokines of the SASP, especially interleukin-6 (IL-6). A testable hypothesis now proposed is to modulate the immune system by harnessing the body's ‘inflammatory reflex’ to reduce cytokines. Vagus nerve stimulation can activate T cell immunity by the cholinergic, α7nicotinic acetylcholine receptor agonist (α7nAchR), and suppress IL-6 systemically, as well as other pro-inflammatory cytokines of the SASP, interleukin -1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). The hypothesis predicts that electrical activation of the vagus nerve, with cytokine reduction, in combination with ICIs, would convert an immune resistant (“cold”) tumor to an immune responsive (“hot”) tumor, and halt glioma progression. The hypothesis also envisions cancer as an immune “dysautonomia” whereby a therapeutic intervention, vagus nerve stimulation (VNS), resets the systemic and local cytokine levels. A prospective, randomized, phase II clinical trial, to confirm the hypothesis, is a logical, exigent, next step. Cytokine reduction by VNS could also be useful for other forms of human cancer, e.g., breast, colorectal, head and neck, lung, melanoma, ovarian, pancreatic, and prostate cancer, as the emerging field of “cancer neuroscience” shows a role for neural regulation of multiple tumor types. Because IL-6, and companion pro-inflammatory cytokines, participate in the initiation, progression, spread and recurrence of cancer, minimally invasive VNS could be employed to suppress glioma or cancer progression, while also mitigating depression and/or seizures, thereby enhancing quality of life. The current hypothesis reimagines glioma pathophysiology as a dysautonomia with the therapeutic objective to reset the autonomic nervous system and form an immune responsive state to halt tumor progression and prevent recurrence. VNS, as a novel method to control cancer, can be administered with ICIs, standard therapy, or in clinical trials, combined with emerging immunotherapy: dendritic cell, mRNA, or chimeric antigen receptor (CAR) T cell vaccines. This is for informational purposes only. For medical advice or diagnosis, consult a professional. Generative AI is experimental.