bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022–09–18
twelve papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Cancer Neuroscience: Evidence for a New Hallmark of Cancer.
  2. Insights and opportunities at the crossroads of cancer and neuroscience.
  3. GABAergic signaling beyond synapses: an emerging target for cancer therapy.
  4. Perineural invasion-associated biomarkers for tumor development.
  5. Drug repurposing in cancer neuroscience: From the viewpoint of the autophagy-mediated innervated niche.
  6. YAP1-TEAD1 mediates the perineural invasion of prostate cancer cells induced by cancer-associated fibroblasts.
  7. Basal Cell Carcinoma With Perineural Invasion: A Systematic Review and Pooled Survival Analysis.
  8. Lymph Node Ratio Nomogram-Based Prognostic Model for Resected Distal Cholangiocarcinoma.
  9. Targeting cancer cachexia: Molecular mechanisms and clinical study.
  10. Spinal Nerve Sheath Tumors: Factors Associated with Postoperative Residual and Recurrent Tumors. A Single-Center Experience.
  11. Treat the mind, not just the body for prostate cancer.
  12. Photonic hyperthermia of malignant peripheral nerve sheath tumors at the third near-infrared biowindow.
  1. Adv Biol (Weinh). 2022 Sep;6(9): e2200192
    Cancer Neuroscience: Evidence for a New Hallmark of Cancer.
    Moran Amit.
      
    DOI:  https://doi.org/10.1002/adbi.202200192
  2. Nat Cell Biol. 2022 Sep 12.
    Insights and opportunities at the crossroads of cancer and neuroscience.
    Chenchen Pan, Frank Winkler.
      The biological and pathological importance of mutual interactions between the nervous system and cancer have become increasingly evident. The emerging field of cancer neuroscience aims to decipher key signalling factors of cancer-nervous system crosstalk and to exploit these modulators as targets for improved anticancer therapies. Here we discuss the key achievements in cancer neuroscience research, inspire further interactions on a variety of related research topics, and provide a roadmap for future studies.
    DOI:  https://doi.org/10.1038/s41556-022-00978-w
  3. Trends Cell Biol. 2022 Sep 13. pii: S0962-8924(22)00195-7. [Epub ahead of print]
    GABAergic signaling beyond synapses: an emerging target for cancer therapy.
    De Huang, Peter B Alexander, Qi-Jing Li, Xiao-Fan Wang.
      Traditionally, γ-aminobutyric acid (GABA) is best known for its role as a primary inhibitory neurotransmitter reducing neuronal excitability in the mammalian central nervous system (CNS), thereby producing calming effects. However, an emerging body of data now supports a function for GABA beyond neurotransmission as a potent factor regulating cancer cell growth and metastasis, as well as the antitumor immune response, by shaping the tumor microenvironment (TME). Here, we review the current knowledge on GABA's effects on the function of tumor cells, tumor-immune interactions, and the underlying molecular mechanisms. Since altered GABAergic signaling is now recognized as a feature of certain types of solid tumors, we also discuss the potential of repurposing existing GABAergic agents as a new class of anticancer therapy.
    Keywords:  GABAergic signaling; antitumor immunity; cancer therapy; metastasis; tumor growth
    DOI:  https://doi.org/10.1016/j.tcb.2022.08.004
  4. Biomed Pharmacother. 2022 Sep 12. pii: S0753-3322(22)01080-0. [Epub ahead of print]155 113691
    Perineural invasion-associated biomarkers for tumor development.
    Qi Liu, Zhiming Ma, Qian Cao, Hongyu Zhao, Yu Guo, Tongjun Liu, Jiannan Li.
      Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected in head and neck tumors and pancreatic, prostate, bile duct, gastric, and colorectal cancers. It leads to poor prognostic outcomes and high local recurrence rates. Despite the increasing number of studies on PNI, targeted therapeutic modalities have not been proposed. The identification of PNI-related biomarkers would facilitate the non-invasive and early diagnosis of cancers, the establishment of prognostic panels, and the development of targeted therapeutic approaches. In this review, we compile information on the molecular mediators involved in PNI-associated cancers. The expression and prognostic significance of molecular mediators and their receptors in PNI-associated cancers are analyzed, and the possible mechanisms of action of these mediators in PNI are explored, as well as the association of cells in the microenvironment where PNI occurs.
    Keywords:  Biomarkers; Perineural invasion; Tumor
    DOI:  https://doi.org/10.1016/j.biopha.2022.113691
  5. Front Pharmacol. 2022 ;13 990665
    Drug repurposing in cancer neuroscience: From the viewpoint of the autophagy-mediated innervated niche.
    Jiayan Shi, Jia Xu, Yang Li, Bowen Li, Hui Ming, Edouard C Nice, Canhua Huang, Qifu Li, Chuang Wang.
      Based on the bidirectional interactions between neurology and cancer science, the burgeoning field "cancer neuroscience" has been proposed. An important node in the communications between nerves and cancer is the innervated niche, which has physical contact with the cancer parenchyma or nerve located in the proximity of the tumor. In the innervated niche, autophagy has recently been reported to be a double-edged sword that plays a significant role in maintaining homeostasis. Therefore, regulating the innervated niche by targeting the autophagy pathway may represent a novel therapeutic strategy for cancer treatment. Drug repurposing has received considerable attention for its advantages in cost-effectiveness and safety. The utilization of existing drugs that potentially regulate the innervated niche via the autophagy pathway is therefore a promising pharmacological approach for clinical practice and treatment selection in cancer neuroscience. Herein, we present the cancer neuroscience landscape with an emphasis on the crosstalk between the innervated niche and autophagy, while also summarizing the underlying mechanisms of candidate drugs in modulating the autophagy pathway. This review provides a strong rationale for drug repurposing in cancer treatment from the viewpoint of the autophagy-mediated innervated niche.
    Keywords:  autophagy; cancer neuroscience; cancer treatment; drug repurposing; innervated niche
    DOI:  https://doi.org/10.3389/fphar.2022.990665
  6. Biochim Biophys Acta Mol Basis Dis. 2022 Sep 10. pii: S0925-4439(22)00211-3. [Epub ahead of print] 166540
    YAP1-TEAD1 mediates the perineural invasion of prostate cancer cells induced by cancer-associated fibroblasts.
    Tianyu Shen, Yang Li, Dekun Wang, Yu Su, Gang Li, Zhiqun Shang, Yuanjie Niu, Xiaoyue Tan.
      Perineural invasion (PNI) driven by the tumor microenvironment (TME) has emerged as a key pattern of metastasis of prostate cancer (PCa), while its underlying mechanism is still elusive. Here, we identified increased CAFs and YAP1 expression levels in patients with metastatic PCa. In the cultured PCa cell line LNCaP, co-culture with cancer-associated fibroblasts (CAFs) could upregulate YAP1 protein expression. Either ectopic overexpression of YAP1 or co-culture with CAFs could promote the infiltration of LNCaPs towards dorsal root ganglia (DRG). This effect could be blocked using an YAP1 inhibitor. In vivo, overexpression of YAP1 could increase PNI in a mouse model of sciatic nerve tumor invasion. Mechanistically, TEAD1 binds to the NGF promotor and YAP1/TEAD1 activates its transcription and consequently increases NGF secretion. In turn, PCa cells treated with CM from CAFs or stable YAP1 overexpression can stimulate DRG to secrete CCL2. The epithelial-to-mesenchymal transition (EMT) of PCa cells is thus activated via CCL2/CCR2. Overall, our data demonstrate that CAFs can activate YAP1/TEAD1 signaling and increase the secretion of NGF, therefore promoting PCa PNI. In addition, EMT induced by PNI suggests a feedback loop is present between neurons and PCa cells.
    Keywords:  Cancer-associated fibroblast; Perineural invasion; Prostate cancer; Yes-associated protein (YAP1)
    DOI:  https://doi.org/10.1016/j.bbadis.2022.166540
  7. Dermatol Surg. 2022 Sep 07.
    Basal Cell Carcinoma With Perineural Invasion: A Systematic Review and Pooled Survival Analysis.
    Yasmine Abushukur, Yousef Ibrahim, Camilla Cascardo, Jacob Keeley, Thomas Knackstedt.
       BACKGROUND: Perineural invasion (PNI) is considered a high-risk histopathologic feature in many skin cancers. Perineural invasion is a well-known poor prognostic factor of squamous cell carcinoma, but is poorly understood in the context of basal cell carcinoma (BCC).
    OBJECTIVE: To analyze available demographic, clinical, and treatment data for BCC with PNI and the effect of these variables on recurrence patterns, disease progression, and cancer-specific mortality (CSM).
    METHODS: A systematic review and pooled-survival analysis was performed using case reports and series of patients with perineural BCC.
    RESULTS: This review included 159 patients from 49 publications. Of these cases, 57 patients reported at least one recurrence. Where reported, median follow-up time was 31 months for patients without recurrence (n = 79) and 21 months for patients with recurrence (n = 32). The cumulative incidence of CSM at 5 years was 8.5% (95% confidence interval [CI] 0.028-0.186) and the overall five-year survival was 90.9% (95% CI 0.796-0.961).
    CONCLUSION: Male gender, multifocal nerve involvement, presence of clinical symptoms, and PNI detected on imaging are associated with poor prognosis of BCC with PNI. The high rate of disease recurrence and suboptimal cumulative incidence of CSM highlights the importance of early clinical detection, before the onset of symptomatic PNI and multifocal nerve involvement.
    DOI:  https://doi.org/10.1097/DSS.0000000000003593
  8. J Am Coll Surg. 2022 Jun 17.
    Lymph Node Ratio Nomogram-Based Prognostic Model for Resected Distal Cholangiocarcinoma.
    and the Cholangiocarcinoma Multicenter Study Coauthor Group
       BACKGROUND: Several variables have been described as prognostic factors for resected distal cholangiocarcinoma (dCC), including lymph node metastases (N status) and lymph node ratio (LNR). This study aimed to evaluate the prognostic value of LNR on survival and to establish a novel prognostic nomogram to predict the cancer-specific recurrence-free survival (RFS) of dCC.
    STUDY DESIGN: Between December 2006 and September 2020, 415 consecutive patients who underwent pancreaticoduodenectomy (PD) for dCC in 10 centers were identified.Multivariate Cox analysis was used to identify all independent risk factors among several prognostic factors. A nomogram was then developed and assessed by integrating the independent prognostic factors into the model and the concordance index (C-index) was used to evaluate its performance.
    RESULTS: According to Cox regression multivariate analysis, a nomogram based on independent prognostic factor for RFS was performed including LNR 15 (HR 2.442, 95%CI 1.348-4.425, p=0.003), perineural invasion (HR 3.100, 95%CI 1.183-8.122, p=0.025), differentiation grade (HR 2.100, 95%CI 1.172-4.143, p=0.021), and radicality of PD (HR 2.276, 95%CI 1.223-4.234, p=0.009). The C-index of the nomogram, tailored based on the previous significant factors, was 0.8.
    CONCLUSIONS: LNR15 yields a high prognostic efficiency for RFS. The nomogram based on LNR can provide an accurate prognosis assessment for patients with resected dCC.
    DOI:  https://doi.org/10.1097/XCS.0000000000000299
  9. MedComm (2020). 2022 Dec;3(4): e164
    Targeting cancer cachexia: Molecular mechanisms and clinical study.
    Yong-Fei Wang, Zi-Yi An, Dong-Hai Lin, Wei-Lin Jin.
      Cancer cachexia is a complex systemic catabolism syndrome characterized by muscle wasting. It affects multiple distant organs and their crosstalk with cancer constitute cancer cachexia environment. During the occurrence and progression of cancer cachexia, interactions of aberrant organs with cancer cells or other organs in a cancer cachexia environment initiate a cascade of stress reactions and destroy multiple organs including the liver, heart, pancreas, intestine, brain, bone, and spleen in metabolism, neural, and immune homeostasis. The role of involved organs turned from inhibiting tumor growth into promoting cancer cachexia in cancer progression. In this review, we depicted the complicated relationship of cancer cachexia with the metabolism, neural, and immune homeostasis imbalance in multiple organs in a cancer cachexia environment and summarized the treatment progress in recent years. And we discussed the molecular mechanism and clinical study of cancer cachexia from the perspective of multiple organs metabolic, neurological, and immunological abnormalities. Updated understanding of cancer cachexia might facilitate the exploration of biomarkers and novel therapeutic targets of cancer cachexia.
    Keywords:  cancer cachexia; exercise; innervation; interorgan communication; metabolism; muscle wasting
    DOI:  https://doi.org/10.1002/mco2.164
  10. World Neurosurg. 2022 Sep 09. pii: S1878-8750(22)01278-5. [Epub ahead of print]
    Spinal Nerve Sheath Tumors: Factors Associated with Postoperative Residual and Recurrent Tumors. A Single-Center Experience.
    Brian J Park, Jennifer Noeller, Colin Gold, Kirill V Nourski, Girish Bathla, Patrick W Hitchon.
       BACKGROUND: Spinal schwannomas (SS) are usually benign tumors with good prognosis treated by surgical excision. However, a complete resection is sometimes complicated due to factors such as location and configuration. Here the authors sought to identify factors that were associated with incomplete surgical resection (residual) and factors associated with recurrence of tumors.
    METHOD: A retrospective review was conducted of 113 cases of SS treated surgically from 2008 to 2021.
    RESULTS: There were 102 benign tumors, and 2 malignant nerve sheath tumors (MPNST). In the benign SS, 87 had gross total resection (GTR), with 8 cases displaying residual (RES), and 7 recurrent (REC) tumors. There was a significantly higher ratio of cervical and sacral tumors (p=0.008 and p=0.004 respectively), dumbbell and foraminal configuration (p<0.0001 and p=0.0006 respectively), and larger tumor volume (p=0.003) in the RES and REC cohorts compared to GTR. A second operation was performed in two patients in the RES and four patients in the REC cohorts. There was a total complication rate of 6%.
    CONCLUSION: Most benign SS are amenable to GTR in 85% of cases, with excellent prognosis. Patients who had RES or REC disease were more likely to have a cervical or sacral location, a dumbbell or foraminal configuration, and larger tumor volume. Except for one new case, and one recurrent that necessitated a lateral approach, the rest were treated through a posterior approach. At surgery, ultrasonography of the canal is advisable to assure that both intra-and extraspinal components of dumbbell lesions have been entirely removed.
    Keywords:  nerve sheath tumor; schwannoma; spine
    DOI:  https://doi.org/10.1016/j.wneu.2022.08.151
  11. Nature. 2022 09;609(7927): S45
    Treat the mind, not just the body for prostate cancer.
    Laura Vargas-Parada.
      
    Keywords:  Cancer; Health care
    DOI:  https://doi.org/10.1038/d41586-022-02862-x
  12. Elife. 2022 Sep 16. pii: e75473. [Epub ahead of print]11
    Photonic hyperthermia of malignant peripheral nerve sheath tumors at the third near-infrared biowindow.
    Yihui Gu, Zhichao Wang, Chengjiang Wei, Yuehua Li, Wei Feng, Wei Wang, Meiqi Chang, Yu Chen, Qingfeng Li.
      Malignant peripheral nerve sheath tumors (MPNSTs), as typical aggressive sarcomas, typically carry a dismal prognosis. Given the insensitivity of these tumors to traditional chemotherapy and the absence of effective targeted drugs, new therapeutic strategies for efficient MPNSTs treatment are urgently needed. Recently, photothermal therapy (PTT) has demonstrated significant potential in cancer theranostics due to its minimally invasive nature and excellent therapeutic outcomes. However, the passive utilization of photothermal agents (PTAs) with poor target specificity and biocompatibility substantially hinders the clinical translation and application of this method. A unique near-infrared laser at the third biowindow (NIR-III) was utilized for photonic hyperthermia treatment of MPNSTs without PTAs. The superficial locations and relatively high collagen content of MPNSTs ensure the efficiency of photothermal tumor ablation and make the NIR-III laser a suitable therapeutic option that has potential for use in clinical applications. Using human MPNST cell line and xenograft models, it can be found that although the NIR-III photothermal treatment efficiency varied among individuals, which was possibly influenced by different endoplasmic reticulum stress responses (ERSRs), the expected antineoplastic effect was ultimately achieved after adjustment of the power density and radiation duration. The present study provides an intriguing noninvasive therapy for MPNSTs that accelerates the clinical translation of PTT while avoiding the biocompatibility issues arising from PTAs.
    Keywords:  cancer biology; medicine; mouse
    DOI:  https://doi.org/10.7554/eLife.75473
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