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Natural Product-Based Anticancer Drug Development: From Molecular Mechanisms to Therapeutic...
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Natural Product-Based Anticancer Drug Development: From Molecular Mechanisms to Therapeutic Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 1589

Special Issue Editor

Prof. Dr. Su-Yun Lyu

E-Mail Website
Guest Editor
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea
Interests: natural products; cancer immunotherapy; molecular biology; drug development; immunomodulation; precision oncology; translational research; bioactive compounds

Special Issue Information

Dear Colleagues,

Cancer immunotherapy has revolutionized oncological treatment, yet clinical success remains limited, with response rates plateauing around 20%. This modest efficacy, combined with significant adverse effects and high costs, necessitates innovative approaches to enhance therapeutic outcomes. Natural products, which contribute to over 60% of approved anticancer drugs, represent a promising yet underexplored avenue for immunomodulation through diverse mechanisms including checkpoint modulation, macrophage polarization, and immunogenic cell death induction.

The clinical translation of immunomodulatory natural products faces significant challenges due to inadequate preclinical models and complex pharmacological properties. Traditional approaches often fail to predict human responses, creating critical translational gaps. Recent advances in drug development platforms, including three-dimensional culture systems, organoid technology, patient-derived models, and precision medicine approaches, offer new opportunities to overcome these limitations and accelerate the development of natural product-based cancer therapeutics.

From the elucidation of molecular mechanisms to formulation optimization and clinical application, there is growing interest in leveraging natural compounds to enhance immune responses against cancer. The integration of modern pharmaceutical sciences with the traditional use of natural products can create unprecedented opportunities for developing more effective and personalized cancer immunotherapies.

This Special Issue welcomes contributions exploring the development and application of natural product-based anticancer therapeutics with immunomodulatory properties. We invite research on mechanisms of action, novel delivery systems, advanced preclinical models, combination therapies, biomarker discovery, and clinical translation strategies that advance our understanding and application of natural products in cancer immunotherapy.

We look forward to receiving your contributions.

Prof. Dr. Su-Yun Lyu
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural products
  • cancer immunotherapy
  • immunomodulation
  • drug development
  • anticancer agents
  • precision medicine
  • translational research
  • bioactive compounds
  • organoids

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Published Papers (2 papers)

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Review

41 pages, 3751 KB  
Review
Plant-Derived Polyphenols in Cancer Therapy: Bridging Molecular Mechanisms and Bioavailability Toward Clinical Translation
by Syed Arman Rabbani, Shrestha Sharma, Mohamed El-Tanani, Suman Khurana, Manita Saini, Monu Yadav, Rakesh Kumar and Yahia El-Tanani
Pharmaceutics 2026, 18(6), 737; https://doi.org/10.3390/pharmaceutics18060737 (registering DOI) - 13 Jun 2026
Abstract
Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like [...] Read more.
Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article
(This article belongs to the Special Issue Natural Product-Based Anticancer Drug Development: From Molecular Mechanisms to Therapeutic Applications)
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29 pages, 2311 KB  
Review
Distributed Pharmacodynamic Architecture in Multi-Component Herbal Formulations: A Flux-Based Framework for Redox-Heterogeneous Diseases
by Moon Nyeo Park
Pharmaceutics 2026, 18(3), 339; https://doi.org/10.3390/pharmaceutics18030339 - 10 Mar 2026
Cited by 1 | Viewed by 1174
Abstract
Cancer is increasingly recognized as a systems-level disorder characterized not only by genetic alterations but also by persistent dysregulation of stress-adaptive signaling networks integrating inflammation, metabolism, immune modulation, and cellular plasticity. Within this framework, reactive oxygen species (ROS) function as flux-dependent regulators of [...] Read more.
Cancer is increasingly recognized as a systems-level disorder characterized not only by genetic alterations but also by persistent dysregulation of stress-adaptive signaling networks integrating inflammation, metabolism, immune modulation, and cellular plasticity. Within this framework, reactive oxygen species (ROS) function as flux-dependent regulators of signaling fidelity rather than merely cytotoxic byproducts. Therapeutic strategies centered on single high-affinity targets or indiscriminate antioxidant suppression often fail to achieve durable responses in redox-heterogeneous and inflammation-driven malignancies. Multi-component herbal formulations represent chemically diverse systems capable of distributed pharmacodynamic modulation across interconnected signaling nodes and heterogeneous pharmacokinetic exposure profiles arising from multi-constituent absorption kinetics. Ojeoksan (Wu Ji San), a classical East Asian multi-herbal decoction, has accumulated experimental and clinical evidence demonstrating regulatory effects on inflammatory mediators, metabolic homeostasis, mitochondrial stress responses, and immune signaling pathways. Rather than inducing abrupt pathway inhibition, OJS appears to exert graded, parallel modulation across multiple redox-sensitive axes. Here, we reinterpret OJS within a flux-based pharmacological framework, conceptualizing it as a distributed redox-buffering architecture rather than a direct cytotoxic agent. By integrating Korean and Chinese research traditions with systems-level redox modeling and electrochemical perspectives, we propose that multi-component formulations may enhance pharmacodynamic robustness through controlled modulation of ROS amplitude and multi-node buffering while temporally distributing pharmacodynamic signals through multi-component pharmacokinetic synchronization. From a formulation science standpoint, such distributed electrochemical diversity may expand therapeutic tolerance windows and mitigate compensatory pathway escape in chronic inflammatory and therapy-resistant cancers. This perspective supports repositioning multi-herbal formulations as network-aligned pharmacological systems compatible with modern molecular pharmacology formulation-level design principles and rational combination therapy strategies. Full article
(This article belongs to the Special Issue Natural Product-Based Anticancer Drug Development: From Molecular Mechanisms to Therapeutic Applications)
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