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      Frontier progress of the combination of modern medicine and traditional Chinese medicine in the treatment of hepatocellular carcinoma

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          Abstract

          Hepatocellular carcinoma (HCC, accounting for 90% of primary liver cancer) was the sixth most common cancer in the world and the third leading cause of cancer death in 2020. The number of new HCC patients in China accounted for nearly half of that in the world. HCC was of occult and complex onset, with poor prognosis. Clinically, at least 15% of patients with HCC had strong side effects of interventional therapy (IT) and have poor sensitivity to chemotherapy and targeted therapy. Traditional Chinese medicine (TCM), as a multi-target adjuvant therapy, had been shown to play an active anti-tumor role in many previous studies. This review systematically summarized the role of TCM combined with clinically commonly used drugs for the treatment of HCC (including mitomycin C, cyclophosphamide, doxorubicin, 5-fluorouracil, sorafenib, etc.) in the past basic research, and summarized the efficacy of TCM combined with surgery, IT and conventional therapy (CT) in clinical research. It was found that TCM, as an adjuvant treatment, played many roles in the treatment of HCC, including enhancing the tumor inhibition, reducing toxic and side effects, improving chemosensitivity and prolonging survival time of patients. This review summarized the advantages of integrated traditional Chinese and modern medicine in the treatment of HCC and provides a theoretical basis for clinical research.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13020-022-00645-0.

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          Most cited references145

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Hepatocellular carcinoma

            Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.
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              Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial

              In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma.
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                Author and article information

                Contributors
                qiwenxiu0517@163.com
                zhangyuejlcc@163.com
                Journal
                Chin Med
                Chin Med
                Chinese Medicine
                BioMed Central (London )
                1749-8546
                30 July 2022
                30 July 2022
                2022
                : 17
                : 90
                Affiliations
                [1 ]GRID grid.440665.5, ISNI 0000 0004 1757 641X, College of Traditional Chinese Medicine, , Changchun University of Chinese Medicine, ; Changchun, 130117 Jilin China
                [2 ]GRID grid.440665.5, ISNI 0000 0004 1757 641X, Department of Scientific Research, , Changchun University of Chinese Medicine, ; Changchun, 130117 Jilin China
                [3 ]GRID grid.440230.1, ISNI 0000 0004 1789 4901, Department of Integrated Chinese and Western Medicine, , Jilin Cancer Hospital, ; Changchun, 130000 Jilin China
                [4 ]GRID grid.440665.5, ISNI 0000 0004 1757 641X, Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, , Changchun University of Chinese Medicine, ; Changchun, 130117 Jilin China
                Author information
                http://orcid.org/0000-0001-8737-2373
                Article
                645
                10.1186/s13020-022-00645-0
                9338659
                35907976
                67b7729e-3ad2-4fff-9adf-54e290d71cd3
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 21 April 2022
                : 20 July 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100013061, Jilin Scientific and Technological Development Program;
                Award ID: 20210204077YY
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Complementary & Alternative medicine
                traditional chinese medicine,hepatocellular carcinoma,combination therapy,adjuvant therapy,chemotherapy,molecular targeted therapy,multidrug resistance,apoptosis,antitumor,overall survival

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