bims-netuvo 2025-05-11 papers

Mol Cancer. 2025 May 05. 24(1): 133

Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities.

Sirui Huang, Jing Zhu, Linglu Yu, Yan Huang, Yue Hu.

A growing body of research suggests a bidirectional interaction between cancer and the nervous system. Neural cells exert their effects on tumors by secreting neurotransmitters and cell adhesion molecules, which interact with specific receptors on tumor cells to modulate their behavior. Conversely, tumor-secreted factors, particularly including inflammatory factors, can alter neural activity and increase neuronal excitability, potentially contributing to neurological manifestations such as epilepsy. The immune system also serves as a crucial intermediary in the indirect communication between cancer and the nervous system. These insights have opened promising avenues for novel therapeutic strategies targeting both tumors and their associated neurological complications. In this review, we have synthesized the key biological mechanisms underlying cancer-nervous system interactions that have emerged over the past decade. We outline the molecular and cellular pathways mediating this cross-talk and explore the clinical implications of targeting the nervous system to suppress tumor growth and metastasis, mitigate neurological complications arising from cancer progression, and modulate the immune response through neural regulation in the context of cancer therapy.

Keywords: Cancer; Nervous system; Neurobiology of cancer; Oncological therapeutic modalities

DOI: https://doi.org/10.1186/s12943-025-02336-4

Surg Case Rep. 2025 ;pii: 25-0016. [Epub ahead of print]11(1):

Rare Case of Additional Ileocecal Resection for Ascending Colon Cancer with R1 Resection due to Advanced Perineural Invasion.

Yoshiaki Kanemoto, Tomonari Amano, Tomohiro Kurokawa, Tetsuya Tanimoto, Masahiro Amano, Kunihisa Miyazaki.

INTRODUCTION: Perineural invasion (PNI) has been cited as an independent prognostic factor in colorectal cancer. We report the first case of an additional resection after ileocecal resection due to advanced lateral extension of PNI, with a review of the literature.
CASE PRESENTATION: A 67-year-old woman underwent colonoscopy due to positive fecal occult blood. Biopsy revealed a 20-mm type 2 tumor in the ascending colon near the ileocecal valve, which was a poorly differentiated adenocarcinoma. She underwent laparoscopic-assisted ileocecal resection and D3 dissection, and the surgery was completed routinely in which functional end-to-end anastomosis (FEEA) was performed extracorporeally. Postoperative course was good and she was discharged one week postoperatively. The pathology showed AI, type 3, 30 × 23 mm, 40%, por2>sig>tub2, pT3a (SS), int, INFb, v2, ly3, Pn1b, PM1, DM0, pN1. There was widespread cancerous extension along the intermuscular plexus within the intrinsic muscular layer of the ileum, and although grossly separated from the tumor by about 80 mm, the tumor was R1 resected with positive oral margins. Additional anastomotic resection was performed by laparotomy. Intraoperatively, the resected section was submitted to a rapid examination, which was confirmed to be negative, and the surgery was completed. The pathological examination revealed that the resected specimen showed an adenocarcinoma on the ileum side of the anastomosis, which infiltrated and proliferated within the intermuscular plexus by about 15 mm, although the tumor was not visually recognized on the resection specimen. Both bilateral margins were negative, resulting in R0 resection. Postoperative adjuvant chemotherapy was not requested by the patient. Thereafter, periodic imaging follow-up was performed and, nine months after the initial diagnosis, there was no increase in tumor markers and no evidence of recurrence on imaging.
CONCLUSIONS: Preventing R1 resection due to lateral extension of advanced PNI, which is very rare as in this case, is practically difficult given its frequency and residual bowel function. Instead, prompt additional resection and adjuvant therapy (which was not performed in this case) are essential to minimize the risk of recurrence.

Keywords: R1 resection; additional resection; adjuvant chemotherapy; ascending colon cancer; lateral progression; perineural invasion

DOI: https://doi.org/10.70352/scrj.cr.25-0016

FASEB Bioadv. 2025 May;7(5): e70004

Tumor innervation in cervical cancer: Prognostic insights from myelin-associated risk signatures.

Guoqiang Chen, Zhen Zheng, Qingqing Ji, Ruihua He, Zhouyuan Pan, Yunxia Chen, Yuqing Zhou, Zhihong Wei, Hao Sun, Lixia Feng.

The reported frequencies of perineural invasion (PNI) in human cervical cancer, ranging from 7.0% to 35.1%, may underestimate the significant role that nerves play in cervical cancer progression. Neurosecretory factors can promote tumor migration and invasion, even in cases classified as "PNI-negative". This study aimed to clarify whether tumor innervation influences tumor progression and cervical cancer patient outcomes. We first evaluated the gene signatures of human myelinating Schwann cells (SCs) using the Inferring Pathway Activity and Suppression (IPAS) scoring system to predict the degree of tumor innervation in 304 cervical cancer patients from The Cancer Genome Atlas (TCGA) database. Subsequently, we constructed a myelin-associated risk prognostic signature using LASSO regression analysis. Finally, we obtained a risk score using a quantitative formula and categorized all samples into high- and low-risk score groups. Our results indicated that tumor innervation in cervical cancer is associated with poor patient survival. Higher levels of innervation were correlated with an impaired immune response and reduced expression of immune checkpoints, including PD-L1. The prognostic model demonstrated excellent consistency between predicted and actual survival outcomes. Overall, tumor innervation plays a crucial role in regulating cervical cancer prognosis. The identified prognostic risk signatures offer a valuable tool for risk stratification and prognostic prediction in clinical practice.

Keywords: Schwann cells; cervical cancer; myelinating; prognosis; tumor innervation

DOI: https://doi.org/10.1096/fba.2024-00190

Neuron. 2025 May 07. pii: S0896-6273(25)00292-2. [Epub ahead of print]113(9): 1307-1309

The nervous system and cancer: A grand challenge and a call to collaborate.

Gabriela Carreno, Gemma M Balmer, Rebecca L Eccles.

Cancer Grand Challenges recently announced seven new challenges, inviting the global research community to assemble multinational interdisciplinary teams to take them on. By including a challenge focusing on the nervous system and cancer, we hope to deepen existing ties between cancer and neuroscience research, entice new thought leaders into the field, and make radical progress together.

DOI: https://doi.org/10.1016/j.neuron.2025.04.009

Acad Radiol. 2025 May 02. pii: S1076-6332(25)00299-5. [Epub ahead of print]

Mismatch Repair Status and Clinico-radiological Feature-Based Model for Pre-treatment Evaluation of Perineural Invasion and Prognosis in Stage I-III Rectal Cancer.

Xiangchun Liu, Lijuan Wan, Rui Zhao, Shuang Chen, Wenjing Peng, Fan Yang, Hongmei Zhang.

RATIONALE AND OBJECTIVES: To develop and validate a predictive model for the pre-treatment evaluation of perineural invasion (PNI) status and to examine its prognostic stratification effectiveness in patients with stage I-III rectal cancer (RC) based on mismatch repair (MMR) status, clinical data, and magnetic resonance imaging (MRI) evaluated features.
MATERIALS AND METHODS: This retrospective study included 815 patients with stage I-III RC who underwent MRI scans from January 2016 to November 2023 and were randomly assigned to the training and validation cohorts. MMR status, clinical data, and MRI-evaluated features associated with PNI status were identified as independent predictors for developing a predictive model by univariable and multivariable logistic regression analyses in the training cohort. The receiver operating characteristic curves and the area under the curves (AUCs) were utilized to evaluate the diagnostic performance of the prediction model in both the training and validation cohorts. The Kaplan-Meier survival curves and Cox proportional hazards regression analysis were utilized to evaluate the prognostic stratification value of the model in both the training and validation cohorts.
RESULTS: The predictive model developed with independent predictors, including deficient MMR (odds ratio [OR]=0.434, P=0.021), male gender (OR=1.578, P=0.013), MRI-evaluated tumor morphology (partly annular, OR=3.257, P<0.001; annular, OR=5.184, P<0.001), tumor stage (T3, OR=1.953, P=0.004; T4, OR=2.627, P=0.013), extramural vascular invasion (OR=1.736, P=0.041), tumor deposit (OR=3.902, P<0.001) and mesorectal fascia involvement (OR=2.679, P=0.023), achieved AUCs of 0.748 (95% confidence interval [CI]: 0.711-0.785, P<0.001) and 0.719 (95% CI: 0.640-0.798, P<0.001) in the training and validation cohorts, respectively. The Kaplan-Meier survival curves show effectively prognostic stratification for disease-free survival (DFS), distant metastasis-free survival (DMFS), and recurrence-free survival (RFS) between predicted PNI-positive and PNI-negative patients (both P<0.05). Cox regression analysis indicated that predicted PNI-positive status was a significant risk factor associated with inferior DFS and DMFS in both training and validation cohorts (both P<0.05). The predicted PNI-positive status was a significant risk factor associated with inferior RFS in the training cohort (P=0.002); however, no significant association was observed in the validation cohort (P=0.104).
CONCLUSION: The developed prediction model for evaluating the PNI status of RC prior to treatment showing acceptable performance and helping with prognostic stratification, which may assist in personalized treatment decisions.

Keywords: Magnetic resonance imaging; Mismatch repair; Perineural invasion; Prognosis; Rectal cancer

DOI: https://doi.org/10.1016/j.acra.2025.03.056