bims-netuvo 2026-06-14 papers

Neoplasia. 2026 Jun 08. pii: S1476-5586(26)00052-7. [Epub ahead of print]78 101322

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Zhendong Zhang, Yunlong Jia, Tianxu Liu, Sheng Wang, Lihua Liu.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create a highly immunosuppressive landscape. Conversely, we investigated the retrograde axis and established that tumor-excreted biochemicals act as potent neuromodulatory agents. Rather than functioning as mere metabolic byproducts, these molecules structurally and functionally remodel intratumoral nerve endings, lowering neuronal firing thresholds and solidifying a self-amplifying loop that drives disease aggression while triggering systemic neurological disorders in the host. Ultimately, dismantling this deleterious alliance is imperative for clinical progress. By integrating neuropharmacological interventions - such as autonomic blockade - with targeted metabolic disruption, we present a dual-pronged translational framework designed to uncouple neuro-metabolic interdependencies, thereby abrogating tumor resilience and alleviating comorbid neuropathologies.

Keywords: Cancer neuroscience; Metabolic reprogramming; Neuro-metabolism; Neurotransmitters; Tumor microenvironment

DOI: https://doi.org/10.1016/j.neo.2026.101322

Cell Oncol (Dordr). 2026 Jun 10. pii: 86. [Epub ahead of print]49(3):

Onco-neurology: a clinical perspective on cancer-associated neurological complications.

Yaying Song, Wenbin Wan, Ying Zhang, Gang Wang.

Advances in cancer screening and treatment have improved survival, while neurological complications in patients with cancer are gaining clinical relevance. Many of these complications are not attributable to direct tumor invasion, compression, or metastasis, but rather reflect immune-mediated mechanisms, treatment exposure, systemic disturbances, or tumor-associated biological processes. They are commonly discussed under categories such as paraneoplastic neurological syndromes, treatment-related neurotoxicity, immune-related adverse events, or related disorders. However, these categories often overlap and require integrated assessment across oncology and neurology. In this Correspondence, we propose "onco-neurology" as a term to describe cancer-associated neurological complications that extend beyond direct nervous system involvement. This concept complements neuro-oncology and paraneoplastic neurological syndromes by emphasizing treatment-related, immune-mediated, systemic, and mixed neurological disorders. Recognition of this field may reduce diagnostic fragmentation, support multidisciplinary evaluation, and promote tumor-immune-neural research.

Keywords: Cancer-associated neurological complications; Immune-related adverse events; Neurotoxicity; Onco-neurology; Paraneoplastic neurological syndromes

DOI: https://doi.org/10.1007/s13402-026-01234-1

iScience. 2026 Jun 19. 29(6): 116153

Neural cues differentially modulate colorectal cancer cell behavior depending on patients' genomic background.

Meike S Thijssen, Rosaria Chilà, Giovanni Crisafulli, Kim M Smits, Alberto Bardelli, Werend Boesmans, Veerle Melotte.

While neurons are mostly described as pro-tumorigenic and linked with a poor prognosis, differing outcomes have been reported for colorectal cancer (CRC) due to the lack of control for neural and patient subtype diversity. In this study, we investigated the effect of neural cues on patient-derived CRC cell lines selected based on genomic status, e.g., microsatellite instability (MSI) and KRAS and BRAF mutations. Although most neural signals increased clonogenicity, the adrenergic neurotransmitter epinephrine had the opposite effect. Epinephrine also decreased CRC cell viability, independent of the genomic status. Vasoactive intestinal peptide decreased cell viability only in BRAF wild-type cells. Interestingly, all neural signals induced migration in microsatellite stable (MSS) cells, with no effect in cells with MSI. Epinephrine or glial cell line-derived neurotrophic factor also stimulated migration specifically in BRAF-mutated cells. These results emphasize the importance of targeting specific neural signaling pathways and highlight that patient stratification is essential for cancer neuroscience studies.

Keywords: microenvironment; neuroscience; oncology

DOI: https://doi.org/10.1016/j.isci.2026.116153

J Adv Res. 2026 Jun 11. pii: S2090-1232(26)00454-6. [Epub ahead of print]

The impact of stress on cancer immunotherapy: from mechanistic insights to intervention strategies.

Zhijie Wang, Jiali Yao, Yuanyuan Zhang, Jin Ding.

BACKGROUND: Immunotherapy has achieved significant breakthroughs in cancer treatment, but its clinical efficacy remains limited in many patients. Concurrently, epidemiological studies indicate that many cancer patients suffer from mental and emotional stress, which may suppress antitumor immunity and weaken immunotherapy efficacy.
AIM OF REVIEW: While existing literature predominantly focuses on how stress promotes general tumor progression by remodeling the local tumor microenvironment (TME), a critical knowledge gap remains regarding its specific impact on immunotherapy. To complement this line of research, this review aims to bridge this gap by explicitly shifting the focus to how stress compromises cancer immunotherapy. It expands the analytical perspective from purely localized tumor niches to the systemic immune macroenvironment to propose mechanistically-driven intervention strategies.
KEY SCIENTIFIC CONCEPTS OF REVIEW: This review systematically dissects how the sympathetic nervous system (SNS), hypothalamic-pituitary-adrenal (HPA) axis, and diverse neurometabolites impair therapeutic efficacy. Mechanistically, it details how these neuroendocrine pathways induce local immunosuppression within the TME and drive systemic immune dysregulation. Crucially, the review highlights how stress-induced dysfunction in immune organs (e.g., bone marrow, thymus, and spleen) and distant non-immune organs (e.g., liver and intestines) collectively compromises cancer immunotherapy. Finally, strategies targeting these pathways are proposed to potentiate immunotherapy efficacy. An emphasis is placed on personalized combination therapies that integrate pharmacological and behavioral interventions aimed at synergizing with immune checkpoint inhibitors, thereby providing novel insights for future research.

Keywords: Cancer immunotherapy; Neuroendocrine-immune axis; Stress

DOI: https://doi.org/10.1016/j.jare.2026.06.004

Neurooncol Adv. 2026 Jun;8(Suppl 4): iv40-iv59

Focused ultrasound for brain metastases.

Ahmad Ozair, Bilal Moiz, Pavlos Anastasiadis, Dheeraj Gandhi, Bibhas Amatya, Michael W McDermott, Graeme F Woodworth, Manmeet S Ahluwalia.

Brain metastases (BMs) increasingly represent a significant cause of morbidity and mortality in cancer patients. The efficacy of systemic therapies for BMs, in contrast to extracranial metastases (EMs), remains limited secondary to a host of challenges. These include insufficient drug delivery due to the blood-brain barrier and blood-tumor barrier, the unique immunological milieu in the tumor microenvironment and cerebrospinal fluid, the diversity of immunogenomic landscapes in BMs across genetically distinct malignancies, the branching evolution of BM from EMs, and the challenges in longitudinally obtaining information regarding clinically actionable genetic alterations in BMs for precision oncology. These complex, long-standing challenges require treatment strategies that address multiple problems concurrently, as represented by the potential of focused ultrasound (FUS) for enhancing effectiveness of several existing BM-specific management strategies. Beyond historically investigated applications of FUS for BMs, including thermoablation and histotripsy, new frontiers include enhanced drug delivery of systemic therapies, plasma sono-liquid biopsy of BM-derived factors, radiosensitization, and immunomodulation. These applications, as discussed here, enable multiple combinatorial opportunities of FUS with targeted- and/or immunotherapies for BMs. With multiple ultrasound delivery platforms (including MR-guided, neuro-navigation-guided, and implantable devices) being investigated in neuro-oncology trials worldwide, this review provides strategies for designing and optimizing future research efforts.

Keywords: acoustics; brain metastasis; microbubble; neuro-oncology; sonication

DOI: https://doi.org/10.1093/noajnl/vdaf131