Lung Cancer Research and Clinical Management in 2026: Precision Oncology, Immunotherapy, and Emerging Signals From Drug Repurposing

By Editorial Team

Abstract

Lung cancer remains the leading cause of cancer mortality worldwide despite rapid progress in precision oncology and immunotherapy. The year 2025 marked a convergence of advances across molecular diagnostics, artificial intelligence–driven pathology, novel targeted and immune-based therapeutics, and increased interest in real-world drug repurposing strategies. Alongside regulatory approvals of next-generation targeted agents and bispecific immunotherapies, observational data have emerged describing the off-label use of antiparasitic agents—fenbendazole, ivermectin, and mebendazole—as adjunctive interventions in lung cancer. This integrative review synthesizes validated clinical and translational advances with mechanistic and real-world observations on repurposed anthelmintics, critically appraising their biological plausibility, evidence limitations, and implications for future research. The analysis highlights the widening gap between innovation and evidence generation, underscoring the need for adaptive trial designs, in-silico modeling, and controlled translational studies.

1. Introduction

Lung cancer, encompassing non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), remains responsible for more cancer-related deaths than any other malignancy. Over the past decade, survival gains have largely been driven by molecular stratification and immune checkpoint inhibition. In 2025, progress accelerated further through artificial intelligence–assisted diagnostics, antibody–drug conjugates (ADCs), bispecific immune therapies, and increasingly individualized treatment pathways.

Parallel to these advances, a growing number of patients—particularly those with advanced or treatment-refractory disease—have pursued off-label and repurposed therapies. Among the most frequently discussed are the antiparasitic agents fenbendazole, ivermectin, and mebendazole. While these agents lack prospective clinical trial validation in lung cancer, their emergence in case series and anecdotal compilations reflects broader dissatisfaction with therapeutic ceilings in late-stage disease and highlights unmet needs not fully addressed by current standards of care.

2. Diagnostic and Predictive Innovations

2.1 AI-Driven Pathology and Imaging

Deep learning approaches applied to label-free histopathology and autofluorescence imaging have demonstrated high accuracy in classifying NSCLC subtypes and predicting immunohistochemical profiles. These technologies offer the potential to reduce diagnostic latency and cost while improving reproducibility.

Generative imaging models capable of synthesizing post-treatment CT scans from baseline imaging and clinical variables have further improved prediction of immunotherapy response, surpassing conventional radiomics in early validation studies. Such models represent a shift from static biomarkers toward dynamic, probabilistic response forecasting.

2.2 Circulating and Multimodal Biomarkers

Liquid biopsy platforms using circulating tumor DNA (ctDNA) have gained traction in both NSCLC and limited-stage SCLC, particularly for monitoring minimal residual disease and guiding consolidation immunotherapy. Integration of ctDNA with imaging, clinical features, and AI-based models reflects an emerging multimodal diagnostic paradigm.

3. Therapeutic Advances in 2025

3.1 Targeted Therapies and ADCs

Regulatory approvals in 2025 expanded precision oncology options for lung cancer, including selective HER2 tyrosine kinase inhibitors and next-generation ROS1 inhibitors with central nervous system penetration. Antibody–drug conjugates targeting TROP2 and other surface antigens demonstrated clinically meaningful activity in heavily pretreated NSCLC populations.

3.2 Immunotherapy and Bispecific Agents

Checkpoint inhibitors remain foundational in NSCLC across early-stage, perioperative, and metastatic settings. In SCLC, bispecific T-cell–engaging antibodies targeting DLL3 achieved full regulatory approval following survival benefits in relapsed disease—an unprecedented milestone in a historically treatment-resistant malignancy.

Checkpoint inhibitors and bispecific antibodies—remain cornerstones of treatment for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Updated clinical evidence supports the use of perioperative immunotherapy, which has improved pathologic response rates and event-free survival in resectable NSCLC. (Cancer Advisor) 

Combination strategies pairing immunotherapy with anti-angiogenic agents, ADCs, or novel immune modulators further reflect a shift toward multi-axis tumor and immune system targeting.

4. Repurposed Anthelmintics in Lung Cancer: Mechanistic Rationale and Observational Evidence

4.1 Biological Plausibility

Preclinical literature provides mechanistic hypotheses for anticancer activity of several antiparasitic agents:

  • Fenbendazole disrupts microtubule polymerization, impairs glucose uptake through GLUT inhibition, induces oxidative stress, and suppresses tumor cell proliferation in vitro and animal models.

  • Mebendazole, a benzimidazole derivative approved for human use, shares microtubule-targeting properties and demonstrates apoptosis induction, anti-angiogenic effects, and favorable central nervous system penetration.

  • Ivermectin modulates multiple oncogenic signaling pathways, including STAT3, AKT/mTOR, and Wnt/β-catenin, and has demonstrated synergy with chemotherapy and immunotherapy in preclinical systems.

Collectively, these mechanisms overlap with established anticancer targets, lending biological plausibility to further investigation.

4.2 Real-World Case Series and Anecdotal Compilations

In 2025, large compilations of patient-reported outcomes described tumor regression or disease stabilization in lung cancer patients using combinations of fenbendazole, ivermectin, and/or mebendazole, frequently alongside conventional therapies such as chemotherapy, targeted agents, or immune checkpoint inhibitors. These reports include cases of advanced NSCLC with radiographic tumor shrinkage, improved symptom burden, and prolonged disease control beyond expected timelines.

However, these observations derive from uncontrolled, self-selected populations and lack standardized diagnostic confirmation, dosing consistency, toxicity reporting, and comparator arms. Importantly, concurrent standard therapies represent a major confounding factor.

5. Evidence Appraisal and Safety Considerations

5.1 Limitations of Current Evidence

At present, evidence supporting antiparasitic agents in lung cancer remains hypothesis-generating only. No randomized controlled trials, prospective cohort studies, or validated biomarkers confirm efficacy or define optimal dosing. Publication bias, survivorship bias, and regression to the mean cannot be excluded.

5.2 Safety and Regulatory Risks

Fenbendazole is not approved for human use, and unsupervised ingestion has been associated with severe hepatotoxicity and fatal outcomes. Even approved agents such as ivermectin and mebendazole carry dose-dependent risks and potential drug–drug interactions, particularly when combined with systemic anticancer therapies.

From a regulatory and ethical standpoint, off-label use outside structured research frameworks poses significant patient safety concerns.

6. Integrating Repurposing Into Modern Oncology Research

The emergence of FIM regimens highlights structural gaps in oncology drug development rather than validated therapeutic breakthroughs. These observations argue for:

  • Adaptive and pragmatic clinical trials for low-cost repurposed drugs

  • In-silico modeling and N-of-1 trial frameworks to prioritize candidates

  • Translational studies assessing pharmacokinetics, tumor penetration, immune effects, and interaction with checkpoint inhibitors

  • Registry-based real-world evidence with standardized data collection

Such approaches may reconcile patient-driven innovation with scientific rigor.

7. Future Directions

Lung cancer research is increasingly defined by convergence: AI-guided diagnostics, immune-targeted therapies, and systems-level modeling. Repurposed agents, while currently unproven, may serve as valuable probes into tumor metabolism, microtubule dynamics, and immune modulation if studied rigorously. The challenge lies not in suppressing unconventional ideas, but in subjecting them to the same evidentiary standards as mainstream therapeutics.

8. Conclusion

The lung cancer landscape in 2025 reflects unprecedented therapeutic sophistication alongside persistent unmet needs, particularly in advanced disease. Precision medicine and immunotherapy continue to deliver measurable survival gains, while observational reports of antiparasitic drug use underscore patient demand for additional options. Bridging these domains will require disciplined translational science, adaptive trial designs, and ethical stewardship to ensure innovation translates into safe and effective care.


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