bims-netuvo 2025-08-17 papers

Int J Mol Sci. 2025 Jul 22. pii: 7064. [Epub ahead of print]26(15):

Roles of Peripheral Nerves in Tumor Initiation and Progression.

Claudia Giampietri, Elisa Pizzichini, Francesca Somma, Simonetta Petrungaro, Elena De Santis, Siavash Rahimi, Antonio Facchiano, Cinzia Fabrizi.

In recent years, a long list of relevant studies has highlighted the engagement of the nervous system in the fine-tuning of tumor development and progression. Several authors have shown that different types of nerve fibres (sympathetic, parasympathetic/vagal or somatosensory fibres) may contribute to tumor innervation affecting cancer initiation, progression and metastasis. A large presence of nerve fibres is frequently observed in tumors with respect to the corresponding healthy tissues. In this regard, it is worth noting that in some cases a reduced innervation may associate with slow tumor growth in a tissue-specific manner. Current studies have begun to shed light over the role played in this specific process by Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system. SCs observed in cancer tissues share strong similarities with repair SCs that appear after nerve injury. A large body of research indicates that SCs may have a role in shaping the microenvironment of tumors by regulating the immune response and influencing their invasiveness. In this review, we summarize data relevant to the role of peripheral innervation in general, and of SCs in particular, in defining the progression of different tumors: melanoma that originate in the skin with mainly sensory innervation; pancreatic and liver-derived tumors (e.g., pancreatic adenocarcinoma and cholangiocarcinoma) with mainly autonomous innervation. We conclude by summarizing data regarding hepatocarcinoma (with anatomical predominance of small autonomic nerve fibres) in which the potential relationship between innervation and tumor progression has been little explored, and largely remains to be defined.

Keywords: Schwann cells; cholangiocarcinoma; hepatocarcinoma; melanoma; nervous system; pancreatic ductal adenocarcinoma; peripheral nerve

DOI: https://doi.org/10.3390/ijms26157064

Curr Pharm Des. 2025 Aug 13.

Exploring the Neurobiological Mechanisms of Cancer Growth.

Md Sadique Hussain, Mudasir Maqbool, Mohit Agrawal, Amita Joshi Rana, Ayesha Sultana, Nasreen Sulthana, Ajay Singh Bisht, Gyas Khan.

Emerging evidence reveals that interactions between the nervous system and tumor biology significantly influence cancer progression, metastasis, and therapeutic outcomes. This review elucidates the neurobiological mechanisms that underpin tumor development, highlighting the dynamic role of neural components within the tumor microenvironment (TME). Neural signals and structural adaptations in the TME stimulate tumorigenesis and enable cancer cell plasticity, mimicking neurodevelopmental processes. Astrocytic glial cells release neurotrophic factors that support metastatic colonization and enhance tumor cell survival. Notably, cancer cells can establish pseudo-tripartite synapses with neurons, promoting both proliferation and invasion. We explore the cancer-neural network interplay, emphasizing how axonal remodeling, circuit reorganization, and synaptic dysfunction not only drive tumor growth but also contribute to associated symptoms like seizures and chronic pain. Molecularly, mutations such as in PIK3CA and abnormalities in neurotransmitter signaling reveal how neuro-tumors communicate and adapt. Furthermore, metabolic stress responses from tumor cells can activate nociceptive neurons, sustaining malignant progression. Understanding these neurobiological interactions opens avenues for novel therapeutic strategies. Precision neuro-oncology may benefit from targeting neurotrophic signaling, synaptic pathways, and neuronal differentiation programs. Advances in biomarker research from neuro-tumors also contribute to improved diagnostic and prognostic tools. By integrating neuroscience insights into oncological frameworks, we propose a paradigm shift toward therapies that intercept the neural circuitry sustaining malignancies. This neuro-oncological approach holds promise in addressing aggressive cancer phenotypes and improving patient outcomes.

Keywords: Cancer metastasis; neuronal plasticity; neurotrophic factors; synaptic transmission; tumor microenvironment.

DOI: https://doi.org/10.2174/0113816128402718250806151308

Mol Cancer. 2025 Aug 10. 24(1): 215

Integrating neuroscience and oncology: neuroimmune crosstalk in the initiation and progression of digestive system tumors.

Haonan Sun, Tao Wang, Xiangyan Jiang, Mingdou Li, Xiaoe He, Yong Ma, Xiangkai Li, Weilin Jin, Zuoyi Jiao.

Keywords: Cancer neuroscience; Digestive system tumors; Neuro-targeted therapy; Neuroendocrine mediators; Neuroimmune crosstalk; Tumor microenvironment

DOI: https://doi.org/10.1186/s12943-025-02412-9

Biochim Biophys Acta Rev Cancer. 2025 Aug 08. pii: S0304-419X(25)00156-8. [Epub ahead of print]1880(5): 189414

GABAergic signaling in colorectal cancer: Mechanistic insights, tumor microenvironment crosstalk, and therapeutic opportunities.

Donghao Tang, Paola Orlandi, Qijie Li, Arianna Bandini, Guido Bocci.

γ-Aminobutyric acid (GABA) and its receptors have emerged as critical modulators of colorectal cancer (CRC) progression and the tumor microenvironment (TME). Although GABA is traditionally recognized as an inhibitory neurotransmitter in the central nervous system, recent studies have uncovered its complex and sometimes paradoxical roles in cancer biology. In vivo, elevated GABA levels in CRC tissues have been associated with enhanced tumor growth, immune evasion, and metabolic adaptation. In contrast, in vitro studies suggest that exogenous GABA and GABA receptor agonists can inhibit CRC cell proliferation, highlighting a context-dependent role for GABAergic signaling. This duality may stem from variations in GABA receptor subtype expression, tumor-intrinsic metabolic reprogramming, and immune modulation within the TME. A better understanding of these mechanisms may offer new therapeutic opportunities. In this review, we summarize recent advances in the field, focusing on the molecular mechanisms, immune and metabolic interactions, and therapeutic potential of targeting GABAergic signaling in colorectal cancer.

Keywords: Colorectal cancer; GABA; GABA receptor; Tumor microenvironment

DOI: https://doi.org/10.1016/j.bbcan.2025.189414