bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–04–13
four papers selected by
Maksym V. Kopanitsa, Charles River Laboratories



  1. Mol Cancer Res. 2025 Apr 09.
      Nerves are important components of the tumor microenvironment and can regulate the progression of various solid tumors. Tumor innervation (TIN) and perineural invasion (PNI) are the two main modes of interaction between tumors and the nervous system. The former simulates neurogenesis or axonogenesis during neural development, while the latter causes neuroinflammation during nerve injury. As the principal glial cells of the peripheral nervous system (PNS), Schwann cells (SCs) are easily hijacked and utilized by cancer cells due to their high plasticity and versatility. Whether TIN or PNI occurs in a tumor, SCs are believed to be associated with these processes, which indicate that SCs may be a target for cancer neurotherapy. This review focuses on elucidating the interactions between tumors and the PNS and the underlying mechanisms involved. Specifically, we delineated the pivotal role of SCs in TIN, PNI, cancer pain, and the immunosuppressive microenvironment. Furthermore, we compared the advantages and disadvantages of several preclinical trials that have exploited the nervous system to treat cancer and discussed the importance of SCs as a new target in cancer neuroscience research. We hope that this review will contribute to a deeper understanding of the significant involvement of SCs within the tumor-neuroimmune axis, and provide novel insights for innovative antitumor therapies.
    DOI:  https://doi.org/10.1158/1541-7786.MCR-25-0124
  2. Cancer Lett. 2025 Apr 05. pii: S0304-3835(25)00267-8. [Epub ahead of print] 217701
      Lung cancer, which has the highest morbidity and mortality rates worldwide, involves intricate interactions with the nervous system. Research indicates that the nervous system not only plays a role in the origin of lung cancer, but also engages in complex interactions with cancer cells through neurons, neurotransmitters, and various neuroactive molecules during tumor proliferation, invasion, and metastasis, especially in brain metastases. Cancer and its therapies can remodel the nervous system. Despite advancements in immunotherapy and targeted therapies in recent years, drug resistance of lung cancer cells after treatment limits improvements in patient survival and prognosis. The emergence of neuroscience has created new opportunities for the treatment of lung cancer. However, it also presents challenges. This review emphasizes that a deeper understanding of the interactions between the nervous system and lung cancer, along with the identification of new therapeutic targets, may lead to significant advancements or even a revolution in treatment strategies for patients with lung cancer.
    Keywords:  neuro-oncology; neuroactive molecules; neurological complications; tumor microenvironment; tumor neuromodulation
    DOI:  https://doi.org/10.1016/j.canlet.2025.217701
  3. Genome Med. 2025 Apr 11. 17(1): 37
       BACKGROUND: Schwannomas are nerve sheath tumors arising at cranial and peripheral nerves, either sporadically or in patients with a schwannomatosis-predisposition syndrome. There is limited understanding of the transcriptional heterogeneity of schwannomas across genetic backgrounds and anatomic locations.
    METHODS: Here, we prospectively profile by single-cell full-length transcriptomics tumors from 22 patients with NF2-related schwannomatosis, non-NF2-related schwannomatosis, and sporadic schwannomas, resected from cranial and peripheral nerves. We profiled 11,373 cells (after QC), including neoplastic cells, fibroblasts, T cells, endothelial cells, myeloid cells, and pericytes.
    RESULTS: We characterize the intra-tumoral genetic and transcriptional heterogeneity of schwannoma, identifying six distinct transcriptional metaprograms, with gene signatures related to stress, myelin production, antigen presentation, interferon signaling, glycolysis, and extracellular matrix. We demonstrate the robustness of our findings with analysis of an independent cohort.
    CONCLUSIONS: Overall, our atlas describes the spectrum of gene expression across schwannoma entities at the single-cell level and will serve as an important resource for the community.
    Keywords:  NF2; Neurofibromatosis type 2; Schwannoma; Schwannomatosis
    DOI:  https://doi.org/10.1186/s13073-025-01462-4
  4. Cancer Res. 2025 Apr 09.
      Chronic psychological stress is often associated with manifestations of malignant diseases. Identification of modulators regulating the interaction between stress and tumorigenesis could provide potential strategies to ameliorate cancer progression. Here, we observed that chronic stress markedly promoted lung cancer progression. Analysis of the landscape of lncRNA expression indicated that lncRNA HIF1A-AS3 was upregulated in the stressed group and in lung cancer specimens compared to normal tissues. HIF1A-AS3 promoted proliferation and invasion of lung cancer cells both in vitro and in vivo. Mechanistically, HIF1A-AS3 translationally activated HIF-1α via direct interaction with YBX1, stimulating downstream signaling cascades. HIF-1α inversely stimulated HIF1A-AS3 transcription by directly binding to its promoter region. Investigation of the immune microenvironment revealed that macrophage depletion could efficiently abolish the tumor promoting effects of chronic stress. Both chronic stress and HIF1A-AS3 overexpression induced M2-like macrophage polarization in tumor tissues in mice. Conditioned medium from HIF1A-AS3 overexpressing lung cancer cells enhanced the mobility and phagocytic activity of human and murine macrophages. Targeting HIF1A-AS3/HIF-1α signaling, which was aberrantly upregulated in human lung cancer specimens and predictive of poor prognosis, counteracted chronic stress-induced lung cancer progression in vivo. In conclusion, the HIF1A-AS3/HIF-1α positive feedback loop mediates chronic stress-induced lung cancer growth through functional reprogramming of tumor-associated macrophages, suggesting that this axis may serve as a promising diagnostic and therapeutic target for patients with lung cancer suffering from psychological stress.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-24-3481