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A Network Pharmacology Review of Plant-Derived Anticancer Compounds in Lung, Breast, Colorectal and Prostate Cancer
Anna Merecz-Sadowska1, Arkadiusz Sadowski1, Karolina Zajdel2
1Department of Economic and Medical Informatics, University of Lodz, 90-214 Lodz, Poland.
Abstract:
Lung, breast, colorectal and prostate cancer account for over 41% of global cancer incidence and 39% of mortality, yet durable control of advanced disease remains limited. Plant secondary metabolites are promising multitarget leads, but their polypharmacological mechanisms cannot be captured by single-target approaches, and the evidence across these four cancers has not been synthesised within a unified framework. This review provides an integrated comparative analysis of network-pharmacology studies of plant-derived anticancer compounds across the four cancers, cataloguing phytochemical profiles, identifying shared and cancer-specific targets, quantifying the concordance between computational predictions and experimental validation, and appraising the translational gap. A systematic search of biomedical databases (2016-2026) identified 101 peer-reviewed studies (40 breast, 33 colorectal, 24 lung, and 14 prostate) combining network pharmacology with experimental validation. AKT1, EGFR, TP53, STAT3, MAPK1/3, CASP3, and HSP90AA1 recurred as cross-cancer hub genes, with the phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase pathways most frequently implicated. Cancer-specific signatures comprised the androgen receptor in prostate, the oestrogen receptor and human epidermal growth factor receptor 2 in breast, β-catenin/Wnt in colorectal, and the epidermal growth factor receptor/RAS axis with epithelial-to-mesenchymal transition effectors in lung cancer. Flavonoids, terpenoids, alkaloids, and polyphenols predominated. The persistent validation gap remains the principal barrier to translation.
Insights
Plant compounds show promise for treating lung, breast, colorectal, and prostate cancers. Network pharmacology reveals shared and specific targets, but a validation gap hinders clinical translation.
Area of Science:
- Oncology
- Pharmacology
- Computational Biology
Background:
- Lung, breast, colorectal, and prostate cancers cause significant global morbidity and mortality.
- Advanced cancer treatment remains challenging, with limited durable control.
- Plant-derived compounds offer multitarget therapeutic potential, but their complex mechanisms require integrated analysis.
Purpose of the Study:
- To conduct an integrated comparative analysis of network pharmacology studies on plant-derived anticancer compounds across four major cancers.
- To identify shared and cancer-specific molecular targets and phytochemical profiles.
- To evaluate the concordance between computational predictions and experimental validation, and assess the translational gap.
Main Methods:
- Systematic literature search of biomedical databases (2016-2026) for studies combining network pharmacology and experimental validation.
- Analysis of 101 selected peer-reviewed studies focusing on breast, colorectal, lung, and prostate cancers.
- Identification and comparison of phytochemicals, network targets, and pathway involvement.
Main Results:
- Network pharmacology identified recurrent cross-cancer hub genes (e.g., AKT1, EGFR, TP53) and pathways (PI3K/AKT, MAPK).
- Cancer-specific targets included androgen receptor (prostate), estrogen receptor/HER2 (breast), β-catenin/Wnt (colorectal), and EGFR/RAS/EMT (lung).
- Flavonoids, terpenoids, alkaloids, and polyphenols were the predominant phytochemical classes.
Conclusions:
- Network pharmacology provides a unified framework for understanding plant-derived anticancer compound mechanisms across multiple cancer types.
- Shared targets suggest potential for broad-spectrum anticancer agents, while specific targets highlight tailored therapeutic strategies.
- The primary barrier to clinical translation is the persistent gap between computational predictions and experimental validation.
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