上海中医药大学附属曙光医院肿瘤科/肿瘤研究所(上海 201203)
姜沙沙,女,在读硕士生,主要从事中西医防治肿瘤的研究
[ "王炎,女,医学博士,博士生导师。现任上海中医药大学附属曙光医院肿瘤科副主任(主持工作)。入选国家优青、国家青年岐黄学者、上海市曙光计划、上海市青年拔尖人才、上海市青年科技“启明星”、上海市卫生计生系统优秀学术带头人等;兼任中国抗癌协会中西整合神经内分泌肿瘤专业委员会副主任委员,世界中医药学会联合会精准医学专业委员会常务委员,中华中医药学会青年委员会委员,上海市中医药学会肿瘤分会常务委员等。长期从事中西医结合防治肿瘤的临床和基础研究。作为第一负责人主持包括国家自然科学基金等项目5项(优秀青年项目1项、面上和青年项目4项)、省部级项目7项。研究成果获教育部科学进步奖二等奖、中国中西医结合学会科技进步奖二等奖、上海市科技进步奖二等奖、上海市中西医结合科学技术奖三等奖、上海市女医师协会第三届“医树奖”、中华中医药学会李时珍医药创新奖等。发表学术论文100余篇,其中SCI收录40余篇,总影响因子158.662分,单篇最高影响因子为17.694分,他引486余次,单篇引用超过81次。主编专著1部、副主编专著3部,培养硕、博士研究生15名。E-mail:wangyan_sg@126.com" ]
纸质出版日期:2024-03-25,
收稿日期:2023-09-22,
修回日期:2024-01-31,
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姜沙沙,张影茹,王炎.转移性结直肠癌靶向药物的耐药机制及中医药治疗策略[J].上海中医药大学学报,2024,38(02):1-7.
JIANG Shasha,ZHANG Yingru,WANG Yan.Resistance mechanism of targeted drugs in metastatic colorectal cancer and therapeutic strategies of traditional Chinese medicine[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2024,38(02):1-7.
姜沙沙,张影茹,王炎.转移性结直肠癌靶向药物的耐药机制及中医药治疗策略[J].上海中医药大学学报,2024,38(02):1-7. DOI: 10.16306/j.1008-861x.2024.02.001.
JIANG Shasha,ZHANG Yingru,WANG Yan.Resistance mechanism of targeted drugs in metastatic colorectal cancer and therapeutic strategies of traditional Chinese medicine[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2024,38(02):1-7. DOI: 10.16306/j.1008-861x.2024.02.001.
分子靶向治疗是转移性结直肠癌(mCRC)的主要治疗方法之一,联合化学疗法可使患者的总生存期(OS)、无进展生存期(PFS)显著获益。临床常用的分子靶向药物主要包括小分子信号传导抑制剂和大分子单克隆抗体。但靶向治疗后期产生的耐药问题成为临床上治疗的关键难题。研究表明,靶向药物耐药机制可能与多种因素相关,包括表皮生长因子受体(EGFR)、血管内皮生长因子(VEGF)、人表皮生长因子受体-2(HER2)等相关细胞信号通路异常以及肿瘤微环境改变等。近年来,研究发现中医药治疗在逆转靶向药物耐药方面颇有成效。因此,该文对CRC分子靶向治疗耐药机制以及中医药应对策略进行论述,并对逆转靶向耐药的中药及其有效成分进行探讨。
Molecular targeted therapy is one of the main treatment options for metastatic colorectal cancer (mCRC), and combined with chemotherapy, it can provide significant benefits in patients' overall survival (OS) and progression-free survival (PFS). Commonly used molecular targeted drugs in clinic mainly includes small molecule signal transduction inhibitors and large molecule monoclonal antibodies. However, the problem of drug resistance in the later stage of targeted therapy becomes a key challenge for clinic treatment. Studies have shown that the mechanism of targeted drug resistance may be related to a variety of factors, including abnormalities in related cell signaling pathways such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2) and alterations in tumor microenvironment. In recent years, studies have found that traditional Chinese medicine are quite effective in reversing targeted drug resistance. Therefore, this article discusses the mechanisms of drug resistance to molecular targeted therapy in CRC, as well as the coping strategies of traditional Chinese medicine, and discusses the tradional Chinese medicine and its active ingredients that can reverse targeted drug resistance.
靶向治疗结直肠癌耐药中医药
targeted therapycolorectal cancerdrug resistancetraditional Chinese medicine
SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
CIARDIELLO F, CIARDIELLO D, MARTINI G, et al. Clinical management of metastatic colorectal cancer in the era of precision medicine[J]. CA Cancer J Clin. 2022, 72(4): 372-401.
杜飞, 董亚萍, 朴成钢. 结肠癌靶向治疗的研究进展[J]. 生命的化学, 2018, 38(2): 259-266.
DU F, DONG Y P, PU C G. Research progress on targeted therapy of colon cancer[J]. Chemistry of Life, 2018, 38(2): 259-266.
CREMOLINI C, ANTONIOTTI C, ROSSINI D, et al. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial[J]. Lancet Oncol, 2020, 21(4): 497-507.
薛颖, 李琦. 结直肠癌的靶向治疗及其耐药机制[J]. 世界临床药物, 2017, 38(11): 721-726.
XUE Y, LI Q, et al. Targeted therapy of colorectal cancer and its drug resistance mechanism[J]. World Clinical Drug, 2017, 38(11): 721-726.
LI Y, CHEN X, LI W, et al. Combination of AntiEGFR and Anti-VEGF Drugs for the Treatment of Previously Treated Metastatic Colorectal Cancer: A Case Report and Literature Review[J]. Front Oncol, 2021, 11: 684309.
ROSEN L S, JACOBS I, BURKES R. Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars[J]. Target Oncol, 2017, 12(5): 599-610.
TABERNERO J, YOSHINO T, COHN A L, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study[J]. Lancet Oncol, 2015, 16(5): 499-508.
KAWAZOE A, ANDO T, HOSAKA H, et al. Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2021, 6(3): 209-217.
TOMIDA C, YAMAGISHI N, NAGANO H, et al. VEGF pathway-targeting drugs induce evasive adaptation by activation of neuropilin-1/cMet in colon cancer cells[J]. Int J Oncol, 2018, 52(4): 1350-1362.
SINGH S, GOMEZ H J, THAKKAR S, et al. Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition[J]. Int J Mol Sci, 2023, 24(5): 4722.
YOSHINO T, PORTNOY D C, OBERMANNOVÁ R, et al. Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase Ⅲ study[J]. Ann Oncol, 2019, 30(1): 124-131.
WANG Y, LEI F, RONG W, et al. Positive feedback between oncogenic KRAS and HIF-1α confers drug resistance in colorectal cancer[J]. Onco Targets Ther, 2015, 8: 1229-1237.
LOREE J M, DOWERS A, TU D, et al. Expanded low allele frequency RAS and BRAF V600E testing in metastatic colorectal cancer as predictive biomarkers for cetuximab in the randomized CO.17 trial[J]. Clin Cancer Res, 2021, 27(1): 52-59.
LOFT M, SHAPIRO J, LEE M, et al. Compliance with Therapeutic Goods Association prescribing information: weekly or second weekly cetuximab for the treatment of metastatic colorectal cancer[J]. Intern Med J, 2023, 53(9): 1610-1617.
CREMOLINI C, ANTONIOTTI C, LONARDI S, et al. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a randomized phase 2 clinical trial[J]. JAMA Oncol, 2018, 4(4): 529-536.
ARNOLD D, LUEZA B, DOUILLARD J Y, et al. Prognostic and predictive value of primary tumour side in patients with Ras wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials[J]. Ann Oncol, 2017, 28(8): 1713-1729.
MARTINELLI E, CIARDIELLO D, MARTINI G, et al. Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives[J]. Ann Oncol, 2020, 31(1): 30-40.
杨利梅,张影茹,程悦蕾, 等. 靶向表皮生长因子受体治疗结直肠癌的耐药机制及中药研究进展[J]. 上海中医药杂志, 2022, 56(2): 81-86.
YANG L M, ZHANG Y R, CHENG Y L, et al. Resistance mechanism of EGFR targeted therapy for colorectal cancer and research progress of traditional Chinese herbal medicines[J]. Shanghai Journal of Traditional Chinese Medicine, 2022, 56(2): 81-86.
CHANG Y Y, LIN P C, LIN H H, et al. Mutation spectra of RAS gene family in colorectal cancer[J]. Am J Surg, 2016, 212(3): 537-544.
YAEGER R, KOTANI D, MONDACA S, et al. Response to antiEGFR therapy in patients with BRAF non-V600-mutant metastatic colorectal cancer[J]. Clin Cancer Res, 2019, 25(23): 7089-7097.
BOKU S, WATANABE M, SUKENO M, et al. Deactivation of glutaminolysis sensitizes PIK3CA-mutated colorectal cancer cells to aspirin-induced growth inhibition[J]. Cancers (Basel), 2020, 12(5): 1097.
DONG Q, SHI B, ZHOU M, et al. Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12[J]. Front Med, 2019, 13(1): 83-93.
YUAN H H, ZHANG X C, WEI X L, et al. LncRNA UCA1 mediates Cetuximab resistance in Colorectal Cancer via the MiR-495 and HGF/c-MET Pathways[J]. J Cancer, 2022, 13(1): 253-267.
LU Y, ZHAO X, LIU Q, et al. lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling[J]. Nat Med, 2017, 23(11): 1331-1341.
YONESAKA K. HER2-/HER3-Targeting Antibody-Drug Conjugates for Treating Lung and Colorectal Cancers Resistant to EGFR Inhibitors[J]. Cancers (Basel), 2021, 13(5): 1047.
DE CUYPER A, VAN DEN EYNDE M, MACHIELS J P. HER2as a predictive biomarker and treatment target in colorectal cancer[J]. Clin Colorectal Cancer, 2020, 19(2): 65-72.
TAKEGAWA N, YONESAKA K. HER2 as an emerging oncotarget for colorectal cancer treatment after failure of anti-epidermal growth factor receptor therapy[J]. Clin Colorectal Cancer, 2017, 16(4): 247-251.
YONESAKA K, ZEJNULLAHU K, OKAMOTO I, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab[J]. Sci Transl Med, 2011, 3(99): 99ra86.
TAKEGAWA N, YONESAKA K, SAKAI K, et al. HER2 genomic amplification in circulating tumor DNA from patients with cetuximab-resistant colorectal cancer[J]. Oncotarget, 2016, 7(3): 453-460.
BERTOTTI A, MIGLIARDI G, GALIMI F, et al. A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer[J]. Cancer Discov, 2011, 1(6): 508-523.
PIETRANTONIO F, ODDO D, GLOGHINI A, et al. MET-Driven Resistance to Dual EGFR and BRAF Blockade May Be Overcome by Switching from EGFR to MET Inhibition in BRAF-Mutated Colorectal Cancer[J]. Cancer Discov, 2016, 6(9): 963-971.
TANG Y, LI D, DUAN J, et al. Resistance to targeted therapy in metastatic colorectal cancer: Current status and new developments[J]. World J Gastroenterol, 2023, 29(6): 926-948.
WOOLSTON A, KHAN K, SPAIN G, et al. Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer[J]. Cancer Cell, 2019, 36(1): 35-50, e9.
LIU N, WU C, JIA R, et al. Traditional Chinese Medicine Combined With Chemotherapy and Cetuximab or Bevacizumab for Metastatic Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial[J]. Front Pharmacol, 2020, 11: 478.
WANG Q, LI Z, GUO J, et al. Effect of Chinese herbal medicine formula on progression-free survival among patients with metastatic colorectal cancer: Study protocol for a multi-center, double-blinded, randomized, placebo-controlled trial[J]. PLoS One, 2022, 17(12): e0275058.
WANG Z, WANG X, LI J, et al. The efficacy and safety of modified Gegenqinlian Fomular for advanced colorectal cancer (damp heat accumulation type): A multicenter randomized controlled trial[J]. Medicine (Baltimore), 2021, 100(49): e27850.
FU X, ZHANG Y, CHANG L, et al. The JPJDF has Synergistic Effect with Fluoropyrimidine in the Maintenance Therapy for Metastatic Colorectal Cancer[J]. Recent Pat Anticancer Drug Discov, 2020, 15(3): 257-269.
CAO B, LI S T, LI Z, et al. Yiqi zhuyu decoction combined with FOLFOX-4 as first-line therapy in metastatic colorectal cancer[J]. Chin J Integr Med, 2011 , 17(8): 593-599.
SUI H, ZHU H R, WU J, et al. Effects of Jianpi Jiedu Recipe on reversion of P-glycoprotein-mediated multidrug resistance through COX-2 pathway in colorectal cancer[J]. Chin J Integr Med, 2014, 20(8): 610-617.
SUI H, PAN S F, FENG Y, et al. Zuo Jin Wan reverses P-gpmediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway[J]. BMC Complement Altern Med, 2014, 14: 279.
周晶,卫真真,浦匀舟, 等. 左金丸逆转KRAS突变型大肠癌西妥昔单抗耐药的作用机制研究[J]. 上海中医药杂志, 2023, 57(5): 37-45.
ZHOU J, WEI Z Z, PU Y Z, et al. Effect and mechanism of Zuojin Wan on reversing cetuximab resistance in KRAS mutant colorectal cancer[J]. Shanghai Journal of Traditional Chinese Medicine, 2023, 57(5): 37-45.
李杰. 乌梅丸对耐西妥昔单抗人结直肠癌细胞的影响及机制研究[D]. 南京:南京中医药大学, 2023.
LI J. Effect and mechanism of umeboshi tablets on cetuximab-resistant human colorectal cancer cells[D]. Nanjing: Nanjing University of Chinese Medicine, 2023.
SUI H, DUAN P, GUO P, et al. Zhi Zhen Fang formula reverses Hedgehog pathway mediated multidrug resistance in colorectal cancer[J]. Oncol Rep, 2017, 38(4): 2087-2095.
杜沅原. 白藜芦醇对结直肠癌获得性西妥昔单抗耐药的逆转及机制研究[D]. 南京:南京医科大学. 2019.
DU R Y. Mechanism ofresveratrol reverse acquired cetuximab resistance in colorectal cancer[D]. Nanjing: Nanjing Medical University, 2019.
HE W T, ZHU Y H, ZHANG T, et al. Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein[J]. Chin J Integr Med, 2019, 25(6): 416-424.
SU P, YANG Y, WANG G, et al. Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells[J]. Int J Oncol, 2018, 53(3): 1343-1353.
LU W D, QIN Y, YANG C, et al. Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo[J]. Clinics (Sao Paulo), 2013, 68(5): 694-701.
WENG W, GOEL A. Curcumin and colorectal cancer: An update and current perspective on this natural medicine[J]. Semin Cancer Biol, 2022, 80: 73-86.
白利平, 康向鹏, 林立,等. 自噬介导的雷公藤甲素提高西妥昔单抗对SW480细胞治疗效果的实验研究[J]. 中国药理学通报, 2019, 35(3): 396-402.
BAI L P, KANG X P, LIN L, et al. Autophagy induced synergistic inhibitory effect of cetuximab in combination with triptolide on proliferation and metastasis of colorectal SW480 cells[J]. Chinese Pharmacological Bulletin, 2019, 35(3): 396-402.
CHEN P, LI X, ZHANG R, et al. Combinative treatment of betaelemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation[J]. Theranostics, 2020, 10(11): 5107-5119.
MI C, CAO X, MA K, et al. Digitoxin promotes apoptosis and inhibits proliferation and migration by reducing HIF-1alpha and STAT3in KRAS mutant human colon cancer cells[J]. Chem Biol Interact, 2022, 51: 109729.
WU H, FAN F, LIU Z, et al. Norcantharidin combined with EGFRTKIs overcomes HGF-induced resistance to EGFR-TKIs in EGFR mutant lung cancer cells via inhibition of Met/PI3k/Akt pathway[J]. Cancer Chemother Pharmacol, 2015, 76(2): 307-315.
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