Targeting tumor innervation: premises, promises, and challenges

Li, Xinyu; Peng, Xueqiang; Yang, Shuo; Wei, Shibo; Fan, Qing; Liu, Jingang; Yang, Liang; Li, Hangyu

doi:10.1038/s41420-022-00930-9

Cited by 34 publications

(21 citation statements)

References 189 publications

(195 reference statements)

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“…In addition, existing neurological drugs can be repurposed to target intratumoral nerves and used alongside traditional chemotherapies. Aside from β-blockers, there is evidence that antidepressant drugs such as selective serotonin reuptake inhibitors, norepinephrine–dopamine reuptake inhibitors and tricyclic antidepressants have anti-tumor effects and prolong patient survival ( Li et al, 2022 ; Zingone et al, 2017 ). Ultimately, a better understanding of the mechanisms of tumor innervation are needed to establish nerve presence as a hallmark of cancer and a viable therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Understanding and modeling nerve–cancer interactions

Oudin

2023

Disease Models &Amp; Mechanisms

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The peripheral nervous system plays an important role in cancer progression. Studies in multiple cancer types have shown that higher intratumoral nerve density is associated with poor outcomes. Peripheral nerves have been shown to directly regulate tumor cell properties, such as growth and metastasis, as well as affect the local environment by modulating angiogenesis and the immune system. In this Review, we discuss the identity of nerves in organs in the periphery where solid tumors grow, the known mechanisms by which nerve density increases in tumors, and the effects these nerves have on cancer progression. We also discuss the strengths and weaknesses of current in vitro and in vivo models used to study nerve–cancer interactions. Increased understanding of the mechanisms by which nerves impact tumor progression and the development of new approaches to study nerve–cancer interactions will facilitate the discovery of novel treatment strategies to treat cancer by targeting nerves.

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Section: Discussionmentioning

confidence: 99%

Understanding and modeling nerve–cancer interactions

Oudin

2023

Disease Models &Amp; Mechanisms

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“…However, targeting TME innervation is relatively new field, and further studies are required to clearly understand the role of nerves in tumor progression. In a recent review, Li et al describes the present status, future perspectives and the associated challenges associated with targeting of tumor innervation [ 79 ].…”

Section: Salient Features Of Tmementioning

confidence: 99%

Tumor microenvironment: barrier or opportunity towards effective cancer therapy

2022

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Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME’s individual components and their interplay at higher resolution. Deeper understanding of the immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a possibility of reprogramming of TME components to overcome the widely prevailing issue of immunotherapeutic resistance. The focus of the present review is to understand the complexity of TME and comprehending future perspective of its components as potential therapeutic targets. The later part of the review describes the sophisticated 3D models emerging as valuable means to study TME components and an extensive account of advanced bioinformatic tools to profile TME components and predict neoantigens. Overall, this review provides a comprehensive account of the current knowledge available to target TME.

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“…Increased tumor innervation in turn regulates angiogenesis, immune and inflammatory and oncogene activation through adrenergic signaling, promoting tumor growth and metastasis [ 138 ]. Not only that, tumor-associated neurons release the calcitonin gene-related peptide (CGRP), which directly increases the exhaustion of CD8 + T-cells and limits their ability to eliminate melanoma [ 139 ].…”

Section: Effects Of Chronic Stress On the Perineural Nerve Of Tumormentioning

confidence: 99%

Chronic stress in solid tumor development: from mechanisms to interventions

et al. 2023

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Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells. Current clinical evidences also suggest that chronic stress affects the outcome of cancer treatment. However, in clinic, there is lack of effective treatment for chronic stress in cancer patients. In this review, we discuss the main mechanisms by which chronic stress regulates the tumor microenvironment, including functional regulation of tumor cells by stress hormones (stem cell-like properties, metastasis, angiogenesis, DNA damage accumulation, and apoptotic resistance), metabolic reprogramming and immune escape, and peritumor neuromodulation. Based on the current clinical treatment framework for cancer and chronic stress, we also summarize pharmacological and non-pharmacological therapeutic approaches to provide some directions for cancer therapy.

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Targeting tumor innervation: premises, promises, and challenges

Cited by 34 publications

References 189 publications

Understanding and modeling nerve–cancer interactions

Understanding and modeling nerve–cancer interactions

Tumor microenvironment: barrier or opportunity towards effective cancer therapy

Chronic stress in solid tumor development: from mechanisms to interventions

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