{"title":"Phytochemicals and their Nanoformulations for Overcoming Drug Resistance in Head and Neck Squamous Cell Carcinoma.","authors":"Zhai Pingping, Chen Nan, Tang Yong","doi":"10.1007/s11095-025-03836-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Drug resistance remains a significant challenge in the treatment of head and neck squamous cell carcinoma (HNSCC), leading to therapeutic failure and poor patient prognosis. Numerous mechanisms, including drug efflux pumps, altered tumor microenvironment (TME), and dysregulated cell death pathways, contribute to the development of resistance against conventional chemotherapeutic agents, immunotherapy, and targeted therapies. As resistance to traditional treatments continues to emerge, there is an urgent need for innovative therapeutic strategies to overcome these challenges. Phytochemicals are naturally occurring bioactive compounds and have demonstrated remarkable potential in targeting multiple resistance mechanisms simultaneously.</p><p><strong>Method: </strong>This review comprehensively overviews the current understanding of drug resistance mechanisms in HNSCC and explores innovative strategies utilizing phytochemicals and their nanoformulations to overcome these resistance mechanisms, with a particular focus on recent developments and future perspectives in this field.</p><p><strong>Results and discussion: </strong>Phytochemicals with anticancer properties include a wide range of herbal-derived molecules such as flavonoids, stilbenes, curcuminoids, alkaloids, traditional Chinese medicine, and others. These compounds can modulate ATP-binding cassette transporters, reverse epithelial-to-mesenchymal transition (EMT), target cancer stem cells (CSCs), and regulate various signaling pathways involved in drug resistance. The integration of phytochemicals into advanced nanoformulation systems has also shown a remarkable improvement in enhancing their bioavailability, stability, and targeted delivery to the TME, potentially improving their therapeutic efficacy. Furthermore, the combination of phytochemicals with conventional chemotherapeutic agents, targeted molecular therapy, and immune checkpoint inhibitors (ICIs) has exhibited synergistic effects, offering a promising approach to restoring drug sensitivity in resistant HNSCC cells.</p><p><strong>Conclusion: </strong>Phytochemicals and their nanoformulations may improve response of HNSCC to therapy by alleviating drug resistance.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11095-025-03836-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Drug resistance remains a significant challenge in the treatment of head and neck squamous cell carcinoma (HNSCC), leading to therapeutic failure and poor patient prognosis. Numerous mechanisms, including drug efflux pumps, altered tumor microenvironment (TME), and dysregulated cell death pathways, contribute to the development of resistance against conventional chemotherapeutic agents, immunotherapy, and targeted therapies. As resistance to traditional treatments continues to emerge, there is an urgent need for innovative therapeutic strategies to overcome these challenges. Phytochemicals are naturally occurring bioactive compounds and have demonstrated remarkable potential in targeting multiple resistance mechanisms simultaneously.
Method: This review comprehensively overviews the current understanding of drug resistance mechanisms in HNSCC and explores innovative strategies utilizing phytochemicals and their nanoformulations to overcome these resistance mechanisms, with a particular focus on recent developments and future perspectives in this field.
Results and discussion: Phytochemicals with anticancer properties include a wide range of herbal-derived molecules such as flavonoids, stilbenes, curcuminoids, alkaloids, traditional Chinese medicine, and others. These compounds can modulate ATP-binding cassette transporters, reverse epithelial-to-mesenchymal transition (EMT), target cancer stem cells (CSCs), and regulate various signaling pathways involved in drug resistance. The integration of phytochemicals into advanced nanoformulation systems has also shown a remarkable improvement in enhancing their bioavailability, stability, and targeted delivery to the TME, potentially improving their therapeutic efficacy. Furthermore, the combination of phytochemicals with conventional chemotherapeutic agents, targeted molecular therapy, and immune checkpoint inhibitors (ICIs) has exhibited synergistic effects, offering a promising approach to restoring drug sensitivity in resistant HNSCC cells.
Conclusion: Phytochemicals and their nanoformulations may improve response of HNSCC to therapy by alleviating drug resistance.
期刊介绍:
Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to:
-(pre)formulation engineering and processing-
computational biopharmaceutics-
drug delivery and targeting-
molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)-
pharmacokinetics, pharmacodynamics and pharmacogenetics.
Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.