bims-netuvo 2025-02-02 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2025–02–02
sixteen papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Sensory neurotransmission and pain in solid tumor progression.
Stress regulatory hormones and cancer: the contribution of epinephrine and cancer therapeutic value of beta blockers.
The role of ketamine and its enantiomer in managing depression and pain in cancer patients: A narrative review.
Mechanisms of Cancer-Induced Bone Pain.
Beta-blockers and epithelial ovarian cancer survival: A Norwegian population-based cohort study.
Schwannoma in the lower inner quadrant of the right breast in a male patient: A rare case report.
UBR5 in Tumor Biology: Exploring Mechanisms of Immune Regulation and Possible Therapeutic Implications in MPNST.
Chronic pain is a risk factor for all-cause and cancer-specific mortality in cancer survivors: a population-based cohort study.
Sympathetic innervation induced by nerve growth factor promotes malignant transformation in gastric cancer.
NEAT1 Promotes the Perineural Invasion of Pancreatic Cancer via the E2F1/GDNF Axis.
Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.
Spatial Profiling Reveals Equivalence-Derived Molecular Signatures of Brain Mimicry and Adaptation in Breast Cancer Brain Metastases.
A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.
Erratum forDoes Colorectal Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer Increase Perineural Invasion?
Halting Pancreatic Ductal Adenocarcinoma Progression and Metastasis by Neuron-Inhibitory Liposomes.
Chronic Stress Mediates Inflammatory Cytokines Alterations and Its Role in Tumorigenesis.

Trends Cancer. 2025 Jan 29. pii: S2405-8033(25)00003-2. [Epub ahead of print]

Sensory neurotransmission and pain in solid tumor progression.

Andre A Martel Matos, Nicole N Scheff.

  Sensory nerves form a crucial component of the tumor microenvironment (TME) that relays vital information to the central nervous system and modulates tumor progression via immunosurveillance. Afferent activity processed by the brain can sensitize brain circuitry and influence host behaviors. Peripheral sensory signaling (e.g., release of neuropeptides in the TME) can drive phenotypic changes in the tumor immune response, such as increased exhaustion markers and inhibited effector cell activity, which promote cancer progression. In this review we highlight the most recent evidence demonstrating the pivotal role of the sensory nervous system in cancer, with a focus on primary tumor pain, and we discuss the extent to which pain can influence cancer progression and treatment response, including immunotherapeutic strategies.

Keywords:  cancer; immunology; immunotherapy; neuroscience; nociception; pain

DOI:  https://doi.org/10.1016/j.trecan.2025.01.003
Endocrine. 2025 Jan 27.

Stress regulatory hormones and cancer: the contribution of epinephrine and cancer therapeutic value of beta blockers.

Rajan Kumar Tiwari, Shiv Govind Rawat, Siddharth Rai, Ajay Kumar.

  The word "cancer" evokes myriad emotions, ranging from fear and despair to hope and determination. Cancer is aptly defined as a complex and multifaceted group of diseases that has unapologetically led to the loss of countless lives and affected innumerable families across the globe. The battle with cancer is not only a physical battle, but also an emotional, as well as a psychological skirmish for patients and for their loved ones. Cancer has been a part of our history, stories, and lives for centuries and has challenged the ingenuity of health and medical science, and the resilience of the human spirit. From the early days of surgery and radiation therapy to cutting-edge developments in chemotherapeutic agents, immunotherapy, and targeted treatments, the medical field continues to make significant headway in the fight against cancer. However, even after all these advancements, cancer is still among the leading cause of death globally. This urges us to understand the central hallmarks of neoplastic cells to identify novel molecular targets for the development of promising therapeutic approaches. Growing research suggests that stress mediators, including epinephrine, play a critical role in the development and progression of cancer by inducing neoplastic features through activating adrenergic receptors, particularly β-adrenoreceptors. Further, our experimental data has also shown that epinephrine mediates the growth of T-cell lymphoma by inducing proliferation, glycolysis, and apoptosis evasion via altering the expression levels of key regulators of these vital cellular processes. The beauty of receptor-based therapy lies in its precision and higher therapeutic value. Interestingly, the enhanced expression of β-adrenergic receptors (ADRBs), namely ADRB2 (β2-adrenoreceptor) and ADRB3 (β3-adrenoreceptor) has been noted in many cancers, such as breast, colon, gastric, pancreatic, and prostate and has been reported to play a pivotal role in facilitating cancer growth mainly by promoting proliferation, evasion of apoptosis, angiogenesis, invasion and metastasis, and chemoresistance. The present review article is an attempt to summarize the available findings which indicate a distinct relationship between stress hormones and cancer, with a special emphasis on epinephrine, considered as a key stress regulatory molecule. This article also discusses the possibility of using beta-blockers for cancer therapy.

Keywords:  Beta-adrenergic receptors; Beta-blockers; Cancer; Epinephrine; Stress; Stress regulatory hormones

DOI:  https://doi.org/10.1007/s12020-025-04161-7
J Anesth Transl Med. 2024 Dec;3(4): 155-165

The role of ketamine and its enantiomer in managing depression and pain in cancer patients: A narrative review.

Michael S Bodnar, Sierra Barber, Heather S L Jim, Jeffery Huang.

  Depression and pain are common comorbidities in cancer patients, and ketamine, a dissociative anesthetic, has shown potential in managing both. This review summarizes current literature on ketamine and its enantiomer, esketamine, in managing depression and pain in the oncologic population. Studies indicate that sub-anesthetic doses of intravenous ketamine and esketamine can alleviate postoperative depressive symptoms in cancer patients with a tolerable safety profile. Research into non-intravenous routes for depression management in the oncologic population remains limited. Ketamine has also proven effective in managing acute postoperative pain, particularly through intravenous administration. While alternative administration routes, such as local infiltration and intramuscular methods, show mixed results, they may provide viable options for patients averse to intravenous (IV). However, the effectiveness of ketamine for chronic cancer pain remains inconsistent. Overall, ketamine offers a promising approach for managing depression and pain in oncologic patients.

Keywords:  Anesthesia; Cancer; Depression; Ketamine; Pain Management

DOI:  https://doi.org/10.1016/j.jatmed.2024.10.005
J Pain Res. 2025 ;18 315-326

Mechanisms of Cancer-Induced Bone Pain.

Xuejuan Wang, Li Li, Yun Wang.

  Bone is a common site of advanced cancer metastasis, second only to the lungs and liver. Cancer-induced bone pain (CIBP) is a persistent and intense pain that is caused by a combination of inflammatory and neuropathic factors. As CIBP progresses, the degree of pain intensifies. Despite advancements in medical technology, the treatment outcomes of patients with CIBP remain unsatisfactory, and severe pain can typically only be controlled with opioid medications. However, patients treated with opioid medications often develop tolerance. Therefore, they may require dose increases, which can increase the severity of opioid-induced side effects, in turn influencing quality of life. The peripheral mechanisms of CIBP primarily involve bone tissue damage, tumor microenvironment formation, and changes in the dorsal root ganglion. The central mechanisms usually involve biochemical and electrophysiological changes in the spinal cord and brain. The spinal cord is the main processing center for nociceptive signals. When tumor cells produce inflammatory mediators that acidify the microenvironment or damage nerve endings, the spinal cord becomes excessively stimulated, resulting in increased or prolonged pain signals that propagate to the higher central nervous system through the ascending pathway. There are substantial differences in the pain generation mechanisms between CIBP and common inflammatory and neuropathic pain. Therefore, understanding the mechanisms underpinning CIBP development at the level of the spinal cord is crucial for optimizing pain management. This study explores the pathogenesis of CIBP at the level of the spinal cord and describes recently proposed treatment methods for CIBP.

Keywords:  Cancer-induced bone pain; astrocyte; microglia; neuron; spinal cord

DOI:  https://doi.org/10.2147/JPR.S498466
Int J Cancer. 2025 Jan 26.

Beta-blockers and epithelial ovarian cancer survival: A Norwegian population-based cohort study.

Leif Lukas Löfling, Nathalie C Støer, Erica K Sloan, Sara Nafisi, Renée Turzanski Fortner, Edoardo Botteri.

  Cancer diagnosis and therapy cause stress to the body. Preclinical studies have shown that stress hormones can stimulate tumor progression and metastasis by interacting with β-adrenergic receptors, and that β-blockers can inhibit those processes. We assessed if β-blocker use was associated with survival in a nationwide cohort of women with epithelial ovarian cancer (EOC). We identified all women aged ≥40 years who underwent EOC surgery in 2004-2018 in Norway through the Cancer Registry of Norway. We estimated the association between peri-diagnostic and post-diagnostic β-blocker use and survival. We used Cox models, adjusted for sociodemographic and health factors, and reported hazard ratios (HRs) and 95% confidence intervals (CIs). The difference in overall survival time between β-blocker users and non-users was estimated as the difference in restricted mean survival time at 5 years after diagnosis using flexible parametric models. We included 3911 women with EOC; 540 (14%) used β-blockers at diagnosis, 1672 (43%) died of the disease, and 1882 (48%) died overall. We found an association between peri-diagnostic β-blocker use and longer EOC-specific survival (HR = 0.85, 95%CI 0.73-1.00; p-value = 0.048), and an indication of an association with overall survival (HR = 0.89, 95%CI 0.77-1.02; p-value = 0.101). Analysis of post-diagnostic β-blocker use, which included only women who survived 12 months or longer (n = 3344), found similar associations. At 5 years from diagnosis, peri-diagnostic β-blocker users lived on average 1.28 months longer than non-users (95%CI 0.01-2.60 months). The results support the hypothesis that β-blocker use improves EOC-specific survival in women with EOC.

Keywords:  beta‐blockers; ovarian cancer; population‐based; registry; survival

DOI:  https://doi.org/10.1002/ijc.35348
Medicine (Baltimore). 2025 Jan 31. 104(5): e41309

Schwannoma in the lower inner quadrant of the right breast in a male patient: A rare case report.

Jingjing Chen, Yan Huang, Haofeng Liu, Yuanyuan Sun, Fufeng Liu.

RATIONALE: Lower inner-quadrant breast schwannomas are exceedingly rare, with no reports of their occurrence in male patients in the literature. In this report, we describe a male patient with a schwannoma in the lower inner quadrant of the right breast.
PATIENT CONCERNS: A 26-year-old man presented at our hospital with a 6-month history of a lump in the right breast and reported pain in the area 3 days prior to presentation. Ultrasonography identified a 0.86 × 0.64 cm hypoechoic nodule 0.41 cm beneath the skin in the lower inner quadrant of the right breast. The nodule exhibited clear boundaries and uniform internal echogenicity with no signs of significant blood flow on color Doppler flow imaging. The patient was concerned that the nodule was benign or malignant.
DIAGNOSES: Histopathological and immunohistochemical analyses after complete surgical excision confirmed that the lesion was breast schwannoma. The postoperative course was unremarkable and the tumor did not recur during 7 years of follow-up.
INTERVENTIONS: Biochemical parameters were examined preoperatively. The radiological examination of breast color Doppler ultrasound was performed.
OUTCOMES: A well-shaped, 0.86 × 0.64 cm mass, complete capsule in the lower inner quadrant of the right breast was surgically resected. The postoperative course was unremarkable and the tumor did not recur during 7 years of follow-up.
LESSONS: Breast schwannoma is an extremely rare tumor that is very difficult to preoperatively diagnose. Preoperative biochemical examination and ultrasonography can only provide diagnostic ideas. Histological and immunohistochemical analyses are required for confirmation. It can transform into malignant peripheral nerve sheath tumors, but not often. Consequently, regular postoperative follow-up is required for such patients, especially ultrasonography.

DOI: https://doi.org/10.1097/MD.0000000000041309
Cancers (Basel). 2025 Jan 07. pii: 161. [Epub ahead of print]17(2):

UBR5 in Tumor Biology: Exploring Mechanisms of Immune Regulation and Possible Therapeutic Implications in MPNST.

Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe.

  Malignant peripheral nerve sheath tumor (MPNST) is a rare but aggressive soft-tissue sarcoma characterized by poor response to therapy. The primary treatment remains surgical resection with negative margins. Nonetheless, in the setting of neurofibromatosis type 1 (NF1), the five-year survival rate is at 20-50%, with recurrence occurring in up to 50% of individuals. For patients with metastatic and unresectable disease, current treatment options include cytotoxic chemotherapy, which offers minimal benefit, and most patients die within five years of diagnosis. Despite advances in targeted therapy focusing on inhibiting Ras signaling and its downstream effectors, clinical trials report minimal clinical benefit, highlighting the need to explore alternative pathways in MPNST pathogenesis. Here, we discuss the role of the E3 ubiquitin ligase, UBR5, in cancer progression and immune modulation across various malignancies, including breast, lung, and ovarian cancer. We focus on mechanisms by which UBR5 contributes to tumorigenesis, focusing on its influence on tumor microenvironment and immune modulation. Additionally, we explore UBR5's roles in normal tissue function, DNA damage response, metastasis, and therapeutic resistance, illustrating its multifaceted contribution to cancer biology. We discuss evidence implicating UBR5 in immune evasion and highlight its potential as a therapeutic target to enhance the efficacy of immune checkpoint blockade (ICB) therapy in MPNST, a tumor typically characterized by an immune cold microenvironment. We outline current immune-based strategies and challenges in MPNST management, ongoing efforts to shift the immune landscape in MPNST, and ultimately, we suggest that targeting UBR5 could be a novel strategy to potentiate ICB therapy-mediated anti-tumor immune response and clinical outcomes, particularly in MPNST patients with inoperable or metastatic disease.

Keywords:  HECT E3 ligases; MPNST; UBR5; immune checkpoint blockade (ICB); immune evasion; immune “cold”; immune “hot”; immunogenicity; neurofibromatosis type 1 (NF1); ubiquitin; ubiquitin proteosome system (UPS)

DOI:  https://doi.org/10.3390/cancers17020161
BMC Public Health. 2025 Jan 25. 25(1): 325

Chronic pain is a risk factor for all-cause and cancer-specific mortality in cancer survivors: a population-based cohort study.

Yeying Zhang, Yuna Guo.

   BACKGROUND: Evidence is lacking on whether chronic pain is related to the risk of cancer mortality. This study seeks to unveil the association between chronic pain and all-cause, cancer, as well as non-cancer death in cancer patients based on the National Health and Nutrition Examination Survey (NHANES) database.
METHODS: Cancer survivors aged at least 20 (n = 1369) from 3 NHANES (1999-2004) cycles were encompassed. Chronic pain and cancer were determined through self-report. We employed records from the National Death Index for the determination of death status and reason. All-cause, cancer, and non-cancer deaths were primary outcomes. We used time-dependent ROC curve assessment to evaluate the predictive value of chronic pain for death in cancer patients.
RESULTS: Over a median 141-month follow-up (interquartile range: 61-201 months), 884 (64.57%) of 1,369 cancer sufferers died, of which 259 (18.91%) died from cancer, and 625 (45.65%) from other causes. Compared with non-chronic pain survivors, chronic pain correlated with elevated all-cause mortality (Hazard Ratio (HR), 1.40; 95% CI, 1.14-1.72, p = 0.001) and cancer death (HR, 1.75; 95% CI, 1.16-2.64, p = 0.008), primarily in patients with pain lasting 3 months or more. Chronic pain was related to higher non-cancer mortality (HR, 1.38; 95% CI, 1.04-1.82, p = 0.025), and no significant results were found in pain duration. Time-dependent ROC curves showed the area under the curve (AUC) for all-cause mortality at 1, 3, 5, 10, and 20-year survival for chronic pain of 0.71, 0.78, 0.84, 0.89, and 0.96, respectively. The AUCs for cancer mortality at 1, 3, 5, 10, and 20-year for chronic pain were 0.83, 0.87, 0.91, 0.94, and 0.95, respectively, and those for non-cancer mortality at 1, 3, 5, 10, and 20-year for chronic pain were 0.82, 0.86, 0.90, 0.91, and 0.97, respectively.
CONCLUSION: Chronic pain is associated with heightened all-cause and cancer mortality in the cancer population. Clinical staff should focus on chronic pain in this patient population.

Keywords:  All-cause mortality; Cancer; Cancer mortality; Chronic pain

DOI:  https://doi.org/10.1186/s12889-025-21406-2
Sci Rep. 2025 Jan 30. 15(1): 3824

Sympathetic innervation induced by nerve growth factor promotes malignant transformation in gastric cancer.

Takefumi Itami, Yukinori Kurokawa, Takaomi Hagi, Shinnosuke Nagano, Rennosuke Nakamoto, Yu Kamakura, Tsuyoshi Takahashi, Takuro Saito, Kazuyoshi Yamamoto, Kota Momose, Kotaro Yamashita, Koji Tanaka, Tomoki Makino, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki.

Sympathetic nerves regulate nearly all human organs. Their peripheral nerves are present in tumor tissue. Activation of the sympathetic nervous system promotes malignant transformation in several cancers. This study aimed to quantify sympathetic nerve density (SND) in gastric cancer and investigate the relationship between SND and nerve growth factor (NGF) in human clinical samples using immunohistochemistry. Patients with high SND in tumor tissue had significantly shorter survival. High NGF expression in tumor tissue was significantly associated with increased SND and poorer prognosis. In vitro studies demonstrated that nerve elongation of PC12 cells, a model for sympathetic neuron-like cells, was promoted by co-culture with gastric cancer cells expressing high NGF levels whereas nerve elongation was suppressed by NGF knockdown. Furthermore, noradrenaline, a neurotransmitter released from sympathetic nerve endings, induced malignant transformation by promoting epithelial-mesenchymal transition, increasing invasiveness and enhancing the ability of gastric cancer cells to migrate. These findings suggest that gastric cancer with high NGF expression might promote sympathetic innervation within tumor tissue, fostering malignant transformation through noradrenaline signaling. Thus, suppressing sympathetic nerve elongation or activation in gastric cancer might be a target for new therapeutic interventions.

DOI: https://doi.org/10.1038/s41598-025-87492-9
Cancer Lett. 2025 Jan 22. pii: S0304-3835(25)00061-8. [Epub ahead of print] 217497

NEAT1 Promotes the Perineural Invasion of Pancreatic Cancer via the E2F1/GDNF Axis.

Jingtao Gu, Qiqi Wang, Jiantao Mo, Tao Qin, Weikun Qian, Wangxing Duan, Liang Han, Zheng Wang, Qingyong Ma, Jiguang Ma.

  Pancreatic cancer is characterized by an insidious onset and high degree of malignancy, with a 5-year survival rate of less than 11%. Perineural invasion (PNI) is one of the pathological features of pancreatic cancer and provides a pathway for distant tumor metastasis, which leads to a poor prognosis. Although NEAT1 promotes the progression of pancreatic cancer, its impact on PNI has not been studied. In this study, we found that NEAT1 facilitates pancreatic cancer metastasis and PNI by regulating E2F1. In vivo experiments showed that NEAT1 promotes PNI in a mouse model. Furthermore, E2F1 is enriched at the promoter region of GDNF and directly participates in its transcriptional regulation. NEAT1 can also recruit P300 to the GDNF promoter region, thereby inducing the H3K27ac modification to further increase chromatin accessibility. This process ultimately facilitates GDNF transcription and tumor innervation, providing a pathway for tumor metastasis.

Keywords:  GDNF; LncRNA; P300; histone modification; perineural invasion

DOI:  https://doi.org/10.1016/j.canlet.2025.217497
Br J Cancer. 2025 Jan 25.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Fang Cheng Wong, Sebastian R Merker, Lisa Bauer, Yi Han, Van Manh Hung Le, Carina Wenzel, Lukas Böthig, Max Heiduk, Pascal Drobisch, Venkatesh Sadananda Rao, Farzaneh Malekian, Ana Mansourkiaei, Christian Sperling, Heike Polster, Mathieu Pecqueux, Rouzanna Istvanffy, Linhan Ye, Bo Kong, Daniela E Aust, Gustavo Baretton, Lena Seifert, Adrian M Seifert, Jürgen Weitz, Ihsan Ekin Demir, Christoph Kahlert.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.
METHODS: EVs were isolated from human/murine PDAC cells, pancreatic stellate cells (PSCs), human tissues and plasma to perform a novel 3D migration assay, qRT-PCR and western blot. Kaplan-Meier and Cox regression analyses were employed to evaluate the clinical potential of plasma EV-derived candidate from 165 PDAC patients.
RESULTS: The EVs from PDAC cells, PSCs derived from human tumour tissues, other cell types in the tumour microenvironment from tumour tissues and circulating plasma act as drivers of a pro-migratory phenotype of SCs by inducing dedifferentiation in SCs. Notably, p75NTR expression was upregulated in the plasma-derived EVs from patients with NI (Pn1) relative to those without NI (Pn0). High expression of plasma-derived EV p75NTR correlated with reduced overall survival and was identified as an independent prognostic factor.
CONCLUSIONS: These findings suggest that EV-mediated SC migration underlies the interactions contributing to PDAC-associated NI with implications for improved outcome and therapeutic strategy.

DOI: https://doi.org/10.1038/s41416-024-02915-0
bioRxiv. 2025 Jan 17. pii: 2025.01.13.631781. [Epub ahead of print]

Spatial Profiling Reveals Equivalence-Derived Molecular Signatures of Brain Mimicry and Adaptation in Breast Cancer Brain Metastases.

Maxine Umeh Garcia, Christine Yiwen Yeh, Bryanna Godfrey, Pablo Nunez Perez, Giuseppe Barisano, Sushama Varma, Saman Ahmadian, Angus Toland, Monica Granucci, Thy Trinh, Hannes Vogel, Robert West, Michael Angelo, Lu Tian, Sylvia K Plevritis, Melanie Hayden Gephart.

Brain metastases (BrMets), common for advanced-stage breast cancer patients, are associated with poor median survival and accompanied by severe neurologic decline. Halting the progression of breast cancer brain metastases (BCBMs) may require modulation of the tumor microenvironment (TME), yet little is known about the impact of the primary breast TME on brain tropism, or how, once there, metastatic breast cancer cells coexist with brain-resident cells (e.g., neurons and glia). Traditionally, studies in this space have focused on differential expression analysis, overlooking potential insights gained from investigating genes with equivalent expression between groups. This is particularly crucial in distant metastasis, where tumor cells may co-opt the transcriptional programs of the host organ (e.g., brain) to facilitate successful seeding and outgrowth. Prior to our work, no computational framework existed to determine biologically-relevant equivalent gene expression. To resolve molecular mechanisms of BCBM enabled by metastatic cancer cells and/or resident brain cells, we leveraged Nanostring GeoMx to perform spatially-resolved transcriptomic profiling on 235 patient-derived tissue cores from BCBM (including adjacent normal brain), primary invasive breast cancers, and normal (non-cancer) brain; analyzing 18,677 RNAs in 450 areas of interest (AOIs). We introduce the "Equivalent Expression Index" a highly specific and accurate algorithm that identifies statistically significant "Equivalently-Expressed Genes". This method facilitated the identification of molecular remodeling and mimicry genes within tissue-specific TMEs. By integrating differential expression analysis with the Equivalent Expression Index, we discovered multiple novel gene signatures associated with BCBM and primary tumor brain-metastatic potential. We demonstrate that the Equivalent Expression Index is a powerful tool to uncover shared gene expression programs representing the adaptation of metastatic cells and brain-resident cells to the BCBM microenvironment.

DOI: https://doi.org/10.1101/2025.01.13.631781
Cancers (Basel). 2025 Jan 08. pii: 180. [Epub ahead of print]17(2):

A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.

Kangwen Xiao, Kuangying Yang, Angela C Hirbe.

  Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive malignancies with a low 5-year survival rate despite current treatments. MPNSTs frequently harbor mutations in key genes such as NF1, CDKN2A, TP53, and PRC2 components (EED or SUZ12) across different disease stages. With the rapid advancement of high-throughput sequencing technologies, the molecular characteristics driving MPNST development are becoming clearer. This review summarizes recent sequencing studies on peripheral nerve sheath tumors, including plexiform neurofibromas (PNs), atypical neurofibromatous neoplasm with uncertain biologic potential (ANNUBP), and MPNSTs, highlighting key mutation events in tumor progression from the perspectives of epigenetics, transcriptomics, genomics, proteomics, and metabolomics. We also discuss the therapeutic implications of these genomic findings, focusing on preclinical and clinical trials targeting these alterations. Finally, we conclude that overcoming tumor resistance through combined targeted therapies and personalized treatments based on the molecular characteristics of MPNSTs will be a key direction for future treatment strategies.

Keywords:  MPNST; RNA-seq; epigenetics; genomics; targeted therapy

DOI:  https://doi.org/10.3390/cancers17020180
J Anus Rectum Colon. 2025 ;9(1): 166

Erratum forDoes Colorectal Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer Increase Perineural Invasion?

Hiroki Kato, Kazushige Kawai, Daisuke Nakano, Akira Dejima, Ichiro Ise, Soichiro Natsume, Misato Takao, Satomi Shibata, Toshiro Iizuka, Tetsuo Akimoto, Yuichiro Tsukada, Masaaki Ito.

[This corrects the article DOI: 10.23922/jarc.2023-057.].

DOI: https://doi.org/10.23922/jarc.E005
Nano Lett. 2025 Jan 28.

Halting Pancreatic Ductal Adenocarcinoma Progression and Metastasis by Neuron-Inhibitory Liposomes.

Zhiqin Wang, Jingyan Wei, Jingyi Sun, Naishi Li, Jingyuan Liu, Yang Huang, Guangjun Nie, Yiye Li.

  Pancreatic ductal adenocarcinoma (PDAC) remains an aggressive malignancy. The occurrence of perineural invasion is associated with neuropathic pain and poor prognosis of PDAC, underscoring the active participation of nerves and their potential as therapeutic targets. Lidocaine is a local anesthetic with antitumor properties in some tumors in the clinic. Nevertheless, its clinical application in PDAC is constrained by the insufficient tumor accumulation and potential neurovirulence associated with a high-dose regimen. Here, a tumor microenvironment-targeted and -responsive liposome was constructed to deliver lidocaine for restraining PDAC growth through single nerve regulation. By conjugation of a collagen binding peptide, the pH-responsive liposomes accumulate in the extracellular matrix. The released lidocaine selectively reduces neurite length and density, thereby indirectly halting the progression and metastasis of PDAC in an orthotopic mouse model without noticeable adverse effects. This study highlights the potential of anesthetic-based nanomodulation of crosstalk between nerve and tumor cells for PDAC treatment.

Keywords:  drug delivery; nanoparticle; neurons; pancreatic ductal adenocarcinoma; tumor microenvironment

DOI:  https://doi.org/10.1021/acs.nanolett.4c05617
J Inflamm Res. 2025 ;18 1067-1090

Chronic Stress Mediates Inflammatory Cytokines Alterations and Its Role in Tumorigenesis.

Zhihan Liu, Meng Lei, Yanxia Bai.

   Introduction: Prolonged psychological stress is closely associated with cancer due to its role in promoting the release of stress hormones through the sustained activation of the sympathetic-adrenal-medullary system. These hormones interact with receptors on inflammatory cells, leading to the activation of key signaling pathways, including the transcription factors signal transducer and activator of transcription 3 (STAT-3) and kappa-light-chain-enhancer of activated B cells (NF-κB). These factors drive the production of pro-inflammatory substances, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which can influence the initiation and progression of cancer.
Purpose: This article aims to summarize how the chronic inflammatory environment induced by chronic stress promotes the initiation, progression, and invasion of cancer. By enhancing our understanding of the complex mechanisms through which stress contributes to cancer, we hope to identify new targets for cancer prevention and treatment.
Conclusion: Chronic stress establishes an inflammatory microenvironment by activating STAT-3 and NF-κB in inflammatory cells. This ongoing inflammation further enhances the activity of these transcription factors, which serve multiple roles: they act as pro-inflammatory agents in inflammatory cells, maintaining chronic inflammation; as oncogenic transcription factors in premalignant cells, promoting cancer initiation; and as pro-differentiation transcription factors in tumor-infiltrating immune cells, facilitating cancer progression. Additionally, the impact of chronic stress varies among different cancer types and individual responses to stress, highlighting the complexity of stress-related cancer mechanisms. Ultimately, this dynamic interplay creates a feedback loop involving IL-6, STAT-3, and TNF-α-NF-κB within the tumor microenvironment, mediating the intricate interactions between inflammation, immunity, and cancer.

Keywords:  IL-6; NF-κB; STAT-3; TNF-α; cancer; inflammation

DOI:  https://doi.org/10.2147/JIR.S485159