Molecular Mechanisms, Evidence Levels, and Translational Prospects of Natural Products in Non-Small Cell Lung Cancer: A Critical Narrative Review
- 1Department of Veterinary Surgery Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand 67210, Sindh, Pakistan.
- 2Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand 67210, Sindh, Pakistan.
Abstract
Non-small cell lung cancer (NSCLC) accounts for approximately 80–85% of lung cancers and remains a major cause of cancer mortality. Molecular heterogeneity, acquired resistance to targeted therapies, immune escape, and treatment-related toxicity continue to limit durable disease control. Natural products and standardized botanical formulations have contributed substantially to anticancer drug discovery and are being investigated as complementary approaches in NSCLC; however, the strength of evidence varies markedly across experimental and clinical settings. This critical narrative review evaluates molecular mechanisms, preclinical evidence, human studies, and translational barriers relevant to natural-product-based interventions in NSCLC. A structured literature update was performed in August 2026 using PubMed/MEDLINE and ClinicalTrials.gov, supplemented by backward reference checking, with emphasis on NSCLC-specific studies and explicit separation of in vitro, animal, observational, randomized, and registry evidence. Preclinical studies indicate that selected compounds can modulate apoptosis and cell-cycle control, context-dependent autophagy, tumor-microenvironment signaling, immune responses, angiogenesis, and metastatic pathways. Human evidence is considerably more limited and is concentrated in EGFR-mutant NSCLC treated with traditional Chinese medicine (TCM) formulations alongside EGFR tyrosine kinase inhibitors (EGFR-TKIs). Translation is further constrained by low or variable bioavailability, dose-dependent toxicity, herb–drug interactions, heterogeneous product composition, and incomplete quality control. Concentrated green-tea extracts and triptolide illustrate that “natural” does not imply low toxicity. Artificial-intelligence-assisted screening and synthesis-aware computational tools may accelerate candidate prioritization, but they do not substitute for pharmacokinetic, toxicological, and prospective clinical validation. Natural products therefore remain promising research candidates and potential adjuncts rather than established replacements for evidence-based NSCLC therapy.
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BibTeX
@article{hussain2026molecular,
title = {{Molecular Mechanisms, Evidence Levels, and Translational Prospects of Natural Products in Non-Small Cell Lung Cancer: A Critical Narrative Review}},
author = {Sakhawat Hussain and Muhammad Yousif and Habibullah Janyaro and Zahid Iqbat Rajput and Mohammad Farooque Hassan},
journal = {Journal of Bioresource Management},
year = {2026},
month = sep,
doi = {10.35691/jbm.6202.0046},
url = {https://doi.org/10.35691/jbm.6202.0046},
note = {CC BY},
}
RIS
TY - JOUR
TI - Molecular Mechanisms, Evidence Levels, and Translational Prospects of Natural Products in Non-Small Cell Lung Cancer: A Critical Narrative Review
AU - Sakhawat Hussain
AU - Muhammad Yousif
AU - Habibullah Janyaro
AU - Zahid Iqbat Rajput
AU - Mohammad Farooque Hassan
PY - 2026
DA - 2026/09/01
JO - Journal of Bioresource Management
DO - 10.35691/jbm.6202.0046
UR - https://doi.org/10.35691/jbm.6202.0046
AB - Non-small cell lung cancer (NSCLC) accounts for approximately 80–85% of lung cancers and remains a major cause of cancer mortality. Molecular heterogeneity, acquired resistance to targeted therapies, immune escape, and treatment-related toxicity continue to limit durable disease control. Natural products and standardized botanical formulations have contributed substantially to anticancer drug discovery and are being investigated as complementary approaches in NSCLC; however, the strength of evidence varies markedly across experimental and clinical settings. This critical narrative review evaluates molecular mechanisms, preclinical evidence, human studies, and translational barriers relevant to natural-product-based interventions in NSCLC. A structured literature update was performed in August 2026 using PubMed/MEDLINE and ClinicalTrials.gov, supplemented by backward reference checking, with emphasis on NSCLC-specific studies and explicit separation of in vitro, animal, observational, randomized, and registry evidence. Preclinical studies indicate that selected compounds can modulate apoptosis and cell-cycle control, context-dependent autophagy, tumor-microenvironment signaling, immune responses, angiogenesis, and metastatic pathways. Human evidence is considerably more limited and is concentrated in EGFR-mutant NSCLC treated with traditional Chinese medicine (TCM) formulations alongside EGFR tyrosine kinase inhibitors (EGFR-TKIs). Translation is further constrained by low or variable bioavailability, dose-dependent toxicity, herb–drug interactions, heterogeneous product composition, and incomplete quality control. Concentrated green-tea extracts and triptolide illustrate that “natural” does not imply low toxicity. Artificial-intelligence-assisted screening and synthesis-aware computational tools may accelerate candidate prioritization, but they do not substitute for pharmacokinetic, toxicological, and prospective clinical validation. Natural products therefore remain promising research candidates and potential adjuncts rather than established replacements for evidence-based NSCLC therapy.
SN - 2309-3854
ER -