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Open research questions in Cancer, Stress, Anesthesia, and Immune Response

103 unresolved questions extracted from the limitations and future-work sections of 277 Cancer, Stress, Anesthesia, and Immune Response papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The need for a comprehensive integration of mechanistic, pharmacologic, and translational evidence. The lack of emphasis on CSC-associated effects and autophagy disruption in prior reviews. The need to critically evaluate exposure-response limitations and biomarker-guided strategies.

    Repurposing Antipsychotic Agents in Oncology: Mechanistic Rationale, Emerging Evidence, and Therapeutic Potential · 2026 · DOI

  • investigate the mechanisms by which propofol influences Wnt–Frizzled-related transcriptional responses, - examine the effects of propofol on other types of cancer cells, - conduct clinical trials to determine the therapeutic potential of propofol in pancreatic cancer treatment, - explore the potential of propofol as a chemotherapeutic agent

    Propofol-Induced Metabolic, Apoptotic, and Wnt–Frizzled-Related Transcript Changes in MIA PaCa-2 Cells: In Vitro and Bioinformatic Analyses · 2026 · DOI

  • The relationship between propofol and Wnt-Frizzled-related transcriptional responses in pancreatic cancer cells is not well understood. The effects of propofol on MIA PaCa-2 cells have not been fully characterized. The clinical evidence for the influence of anesthetic and analgesic exposures on tumor-cell behavior during the perioperative period is unsettled.

    Propofol-Induced Metabolic, Apoptotic, and Wnt–Frizzled-Related Transcript Changes in MIA PaCa-2 Cells: In Vitro and Bioinformatic Analyses · 2026 · DOI

  • There is a lack of direct trials showing that aligning anesthesia, analgesia, and immunonutrition improves recovery through an immune mechanism. Current evidence on the effects of anesthetic and analgesic strategies on immune activity is limited and heterogeneous. There is a need for further research on the relationship between anesthesia, analgesia, and immunonutrition in perioperative immune homeostasis.

    Anesthesia, analgesia, and immunonutrition in perioperative immune homeostasis: a focused mini review · 2026 · DOI

  • Current evidence does not establish clinical anticancer efficacy for CGRP blockade or nociceptor ablation, - Translational development is needed to proceed through pharmacodynamic window studies, tumor-specific biomarker enrichment, and combination trials, - Long-term safety assessment is required, - Oncology dose finding and tumor-response endpoints need to be established

    The CGRP-nociceptor axis in cancer: tumor-specific programs of immune evasion, stromal remodeling, and tumor growth · 2026 · DOI

  • Translational development should proceed through pharmacodynamic window studies, tumor-specific biomarker enrichment, and combination trials, - Studies should measure structural innervation together with neuronal activation, local CGRP release, receptor engagement, and the proposed cellular output, - Research on the role of CGRP in inflammation-associated colorectal tumorigenesis is needed

    The CGRP-nociceptor axis in cancer: tumor-specific programs of immune evasion, stromal remodeling, and tumor growth · 2026 · DOI

  • The complexity of corticosteroid use in oncology, with multiple factors contributing to their negative effects - The need to balance the benefits and risks of corticosteroid use in cancer care - The challenge of developing safer, more effective therapeutic strategies to replace or complement corticosteroids

    Rethinking corticosteroids use in oncology · 2025 · DOI

  • Exploring safer alternatives to CSs, - Investigating dietary interventions, - Examining the effects of renin-angiotensin system blockers and vitamin D optimization

    Rethinking corticosteroids use in oncology · 2025 · DOI

  • Translational investigation, - Development of rational, pathway-directed combination strategies

    Repurposing Antipsychotic Agents in Oncology: Mechanistic Rationale, Emerging Evidence, and Therapeutic Potential · 2026 · DOI

  • Direct trials of integrated anesthesia-analgesia-immunonutrition pathways are now needed to connect these mechanistic pathways with recovery outcomes

    Anesthesia, analgesia, and immunonutrition in perioperative immune homeostasis: a focused mini review · 2026 · DOI

  • We also outline key challenges to clinical translation, such as the spatiotemporal heterogeneity of neuroimmune regulation, the narrow therapeutic window of neuropharmacological agents, and the lack of standardized biomarkers.

    The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications · 2026 · DOI

  • Given that all components of PTM regimens are clinically effective and safe, further clinical studies are warranted.

    Non-steroidal anti-inflammatory drugs (NSAIDs) regimens enhance synergistic selective anticancer efficacy of chemotherapeutic agents on cultured cells · 2025 · DOI

  • Concomitant medications are increasingly recognized for their immunomodulatory properties, yet interactions within complex cancer regimens are underexplored.

    Investigating the influence of baseline medications on immune checkpoint inhibitor treatment outcomes for cancer patients 3706 · 2025 · DOI

  • Neurotransmitter (NT) signaling, known to be immunosuppressive in various disease models, is underexplored in the tumor microenvironment (TME).

    Neurotransmitter modulation of anti-tumor responses: new avenues for enhancing immunotherapy 2602 · 2025 · DOI

  • Abstract Description Early onset colorectal cancer (CRC) incidence rates have significantly increased over the past two decades, but the underlying mechanisms are poorly understood.

    Early life exposure to antidepressants shapes anti-tumor immunity 4527 · 2025 · DOI

  • Chronic stress is a recognized risk factor for tumor progression, but its specific role in TNBC remains unclear.

    Stress-driven tumor-immune interactions in triple-negative breast cancer 4263 · 2025 · DOI

  • While perineural invasion (PNI) is associated with poor prognosis in CRC, the impact of nerve density and diameter on tumor behavior remains unclear.

    Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth · 2025 · DOI

  • However, challenges such as the non-specific nature of SNS blockade and the complexity of TME interactions necessitate further research into ARs subtypes, tumor-specific metabolic vulnerabilities, and predictive biomarkers.

    Sympathetic nervous system in tumor progression and metabolic regulation: mechanisms and clinical potential · 2025 · DOI

  • BACKGROUND: The therapeutic impact of beta-blockers (BB), beta-adrenergic receptor antagonists, on prostate cancer remains controversial.

    Beta-blockers prolong response to androgen deprivation therapy in prostate cancer through modulation of the neuro-immuno-oncology axis · 2025 · DOI

  • BACKGROUND Perioperative blood transfusion is common in gastric cancer surgery, yet its impact on postoperative inflammation, stress response, and long-term prognosis remains incompletely understood.

    Influence of blood transfusion on postoperative inflammation, stress markers, and prognosis in patients with gastric cancer · 2025 · DOI

  • Emerging evidence underscores the critical, yet frequently underrecognized, role of the nervous system in the development and progression of gastric cancer (GC), primarily mediated through complex neuro-tumoral interactions and modulation of immune responses.

    Advances in the study of the relationship between neurotransmitters and gastric cancer · 2025 · DOI

  • However, whether tumor-derived exosomes (TDEs) are influenced by chronic stress and participate in chronic stress-mediated distant metastasis remains unclear.

    Chronic Stress‐Induced and Tumor Derived SP1 + Exosomes Polarizing IL‐1β + Neutrophils to Increase Lung Metastasis of Breast Cancer · 2024 · DOI

  • While preclinical investigations focusing on anesthetics' impact on the behavior of cancer cells are quite convincing, limited clinical trials studying the consequences on survival and recurrences remain inconclusive.

    Perioperative Immunosuppressive Factors during Cancer Surgery: An Updated Review · 2024 · DOI

  • However, the mechanisms underlying its anti-tumor effects have not been fully elucidated.

    Anti-Proliferative Effects of Lidocaine as an Autophagy Inducer in Bladder Cancer via Intravesical Instillation: In Vitro and Xenograft Mouse Model Experiments · 2024 · DOI

  • General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown.

    General anaesthetics reduce acute lymphoblastic leukaemia malignancies in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms · 2024 · DOI

Most-cited papers in Cancer, Stress, Anesthesia, and Immune Response

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103 open questions have been extracted from the limitations and future-work passages of 277 Cancer, Stress, Anesthesia, and Immune Response papers in our 4.5M-paper local library. Each one below links back to the study that raised it, so you can read the original claim in context.

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