Liu H, Jiang WY, Mao FF. Letter to the Editor: Advancing the clinical translation of triptolide and quercetin in hepatocellular carcinoma: A commentary on dual JAK-STAT/mTOR inhibition. World J Gastroenterol 2026; 32(30): 117813 [DOI: 10.3748/wjg.117813]
Corresponding Author of This Article
Fei-Fei Mao, Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 227 Chongqing South Road, Shanghai 200086, China. maofeifei01@126.com
Research Domain of This Article
Oncology
Article-Type of This Article
letter
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Liu H, Jiang WY, Mao FF. Letter to the Editor: Advancing the clinical translation of triptolide and quercetin in hepatocellular carcinoma: A commentary on dual JAK-STAT/mTOR inhibition. World J Gastroenterol 2026; 32(30): 117813 [DOI: 10.3748/wjg.117813]
World J Gastroenterol. Aug 14, 2026; 32(30): 117813 Published online Aug 14, 2026. doi: 10.3748/wjg.117813
Letter to the Editor: Advancing the clinical translation of triptolide and quercetin in hepatocellular carcinoma: A commentary on dual JAK-STAT/mTOR inhibition
Hua Liu, Wei-Yi Jiang, Fei-Fei Mao
Hua Liu, Fei-Fei Mao, Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200086, China
Wei-Yi Jiang, Department of Oncology, Ningbo Municipal Hospital of Traditional Chinese Medicine, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo 315000, Zhejiang Province, China
Co-first authors: Hua Liu and Wei-Yi Jiang.
Author contributions: Liu H and Jiang WY contributed equally as co-first authors; Liu H wrote the original draft; Mao FF contributed to conceptualization, writing, reviewing and editing; Jiang WY participated in drafting the manuscript; all authors have read and approved the final version of the manuscript.
AI contribution statement: The use of AI-assisted tools (specifically Deepseek and ChatGPT for the initial translation, and Grammarly for language polishing) was employed to enhance the readability and language accuracy of the manuscript. However, these tools were not utilized for data analysis or for any writing assistance beyond the scope of polishing. The core writing and scientific argumentation are entirely the author's achievements.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Fei-Fei Mao, Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 227 Chongqing South Road, Shanghai 200086, China. maofeifei01@126.com
Received: December 18, 2025 Revised: January 21, 2026 Accepted: March 6, 2026 Published online: August 14, 2026 Processing time: 217 Days and 3.6 Hours
Abstract
Hepatocellular carcinoma (HCC) is a major global health challenge characterized by high incidence and mortality rates. Although the therapeutic landscape for advanced HCC has been revolutionized by the advent of immune checkpoint inhibitors and tyrosine kinase inhibitors, many patients exhibit primary or acquired resistance, highlighting the urgent need for novel therapeutic strategies. Combination therapy, the cornerstone of modern HCC management, aims to improve treatment efficacy and overcome resistance by targeting multiple oncogenic pathways simultaneously. Tong et al published a study in the World Journal of Gastroenterology provided insights into the mechanistic synergies underlying these approaches and examined the emerging potential of natural products as sources for novel therapeutic agents. They specifically examined the combination of triptolide and quercetin as a promising strategy that leverages synergistic anti-tumor effects while mitigating toxicity. This combination co-targets critical signaling networks, including the Janus kinase/signal transducer and activator of transcription and the mammalian target of rapamycin pathways, which play a key role in hepatocarcinogenesis. In this letter, we discuss the main challenges and future directions for translating such preclinical findings into clinical practice, including the need for more relevant preclinical models that incorporate the tumor microenvironment, advanced drug delivery systems to overcome pharmacokinetic limitations, and the identification of predictive biomarkers to guide personalized therapy.
Core Tip: Tong et al provide a robust preclinical foundation for the combined triptolide and quercetin therapy for hepatocellular carcinoma. They demonstrate synergistic anti-tumor activity through a multi-pathway mechanism where both compounds bind to key proteins like Janus kinase 1, signal transducer and activator of transcription 3, phosphoinositide 3-kinases, and mammalian target of rapamycin, disrupting carcinogenic signaling. This research adds to the growing body of work on natural product-based cancer therapies. To advance this promising start, future investigations using immunocompetent models, detailed pharmacokinetic studies, and deeper mechanistic validation are essential. Such efforts may translate these findings into a viable clinical strategy, aligning with the broader push toward precision medicine in oncology.
