微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

王娜; 韩晓红

doi:10.12290/xhyxzz.2023-0212

微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

doi: 10.12290/xhyxzz.2023-0212

王娜^1,2,
韩晓红^1,2, ,

1 中国医学科学院北京协和医院临床药理研究中心国家药监局药物临床研究与评价重点实验室创新药物临床PK/PD北京市重点实验室, 北京 100730;
2 中国医学科学院北京协和医院疑难重症及罕见病国家重点实验室, 北京 100730

基金项目:

中央高水平医院临床科研专项（2022-PUMCH-B-033）

详细信息

通讯作者:
韩晓红,E-mail: hanxiaohong@pumch.cn

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- 文章访问数: 22
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- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2023-04-26
- 录用日期: 2023-06-15
- 网络出版日期: 2023-07-06

Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug

WANG Na^1,2,
HAN Xiaohong^{1,2
, ,}

1 Clinical Pharmacology Research Center,NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs,Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;
2 State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funds:

National High Level Hospital Clinical Research Funding（2022-PUMCH-B-033）

摘要

摘要: 抗肿瘤药物不断推陈出新，但药物响应率有限及药物不良反应问题严重限制了其临床应用。近年来，“药物微生物组学”概念兴起，越来越多的研究表明，人体微生物菌群在抗肿瘤药物治疗中发挥重要作用。本文从化疗药物、分子靶向药物、免疫治疗药物三方面综述微生物菌群与抗肿瘤药物的相互作用，机制涉及免疫调节、激素水平调节、代谢物水平调节、药物生物转化及跨膜转运调节等，并对可改善抗肿瘤药物疗效及不良反应的微生物菌群调控策略进行概述，以期为临床抗肿瘤药物个体化治疗提供参考。
- 药物微生物组学 /
- 微生物菌群 /
- 抗肿瘤药物 /
- 药物疗效 /
- 药物不良反应
Abstract: Despite the rapid development of antitumor drugs, the limited drug response rate and adverse drug reactions severely limit their clinical application. In recent years, the concept of "pharmacomicrobiomics" has emerged, and more and more studies have shown that the microbiota plays an important role in the treatment of antitumor drugs. Herein, the interaction between microbiota and antitumor drugs was reviewed from the aspects of chemotherapeutics, molecular targeted drugs and immunotherapy drugs, the mechanism involved immune regulation, hormone regulation, metabolite regulation, drug biotransformation and transmembrane transport regulation. The microbiota regulation strategies that can improve the efficacy and reduce adverse reactions of antitumor drugs are reviewed, in order to provide reference for the individualized treatment of clinical antitumor drugs.
- pharmacomicrobiomics /
- microbiota /
- antitumor drugs /
- drug efficacy /
- adverse drug reactions

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参考文献(63)

[1]	Sung H, Ferlay J, Siegel RL, 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: 209-249.
[2]	Zhong L, Li Y, Xiong L, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives[J]. Signal Transduct Target Ther, 2021, 6: 201.
[3]	Roden DM, McLeod HL, Relling MV, et al. Pharmacogenomics[J]. Lancet, 2019, 394: 521-532.
[4]	Jia W, Li H, Zhao L, et al. Gut microbiota: a potential new territory for drug targeting[J]. Nat Rev Drug Discov, 2008, 7: 123-129.
[5]	Alexander JL, Wilson ID, Teare J, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity.[J]. Nat Rev Gastroenterol Hepatol, 2017, 14: 356-365.
[6]	Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J]. Science, 2013, 342: 967-970.
[7]	Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide[J]. Science, 2013, 342: 971-976.
[8]	Daillère R, Vétizou M, Waldschmitt N, et al. Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects[J]. Immunity, 2016, 45: 931-943.
[9]	Li Y, Dong B, Wu W, et al. Metagenomic Analyses Reveal Distinct Gut Microbiota Signature for Predicting the Neoadjuvant Chemotherapy Responsiveness in Breast Cancer Patients[J]. Front Oncol, 2022, 12: 865121.
[10]	Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy[J]. Cell, 2017, 170: 548-563.e16.
[11]	Zhang S, Yang Y, Weng W, et al. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer[J]. J Exp Clin Cancer Res, 2019, 38: 14.
[12]	Logan RM, Stringer AM, Bowen JM, et al. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs[J]. Cancer Treat Rev, 2007, 33: 448-460.
[13]	Bawaneh A, Wilson A S, Levi N, et al. Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer[J]. Cancers(Basel), 2022, 14:4849.
[14]	Panebianco C, Adamberg K, Jaagura M, et al. Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer xenografted mice[J]. Cancer Chemother Pharmacol, 2018, 81: 773-782.
[15]	Huang B, Gui M, Ni Z, et al. Chemotherapeutic Drugs Induce Different Gut Microbiota Disorder Pattern and NOD/RIP2/NF-κB Signaling Pathway Activation That Lead to Different Degrees of Intestinal Injury[J]. Microbiol Spectr, 2022, 10: e0167722.
[16]	Sfanos KS, Markowski MC, Peiffer LB, et al. Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis-targeted therapies[J]. Prostate Cancer Prostatic Dis, 2018, 21: 539-548.
[17]	Pernigoni N, Zagato E, Calcinotto A, et al. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis[J]. Science, 2021, 374: 216-224.
[18]	Clark AR. Anti-inflammatory functions of glucocorticoid-induced genes[J]. Mol Cell Endocrinol, 2007, 275: 79-97.
[19]	Menezes-Garcia Z, Do Nascimento Arifa RD, Acúrcio L, et al. Colonization by Enterobacteriaceae is crucial for acute inflammatory responses in murine small intestine via regulation of corticosterone production[J]. Gut microbes, 2020, 11: 1531-1546.
[20]	Liu H, Wang J, He T, et al. Butyrate: A Double-Edged Sword for Health?[J]. Adv Nutr, 2018, 9: 21-29.
[21]	Panebianco C, Villani A, Pisati F, et al. Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models[J]. Biomed Pharmacother, 2022, 151: 113163.
[22]	Geng H W, Yin FY, Zhang ZF, et al. Butyrate Suppresses Glucose Metabolism of Colorectal Cancer Cells via GPR109a-AKT Signaling Pathway and Enhances Chemotherapy[J]. Front Mol Biosci, 2021, 8: 634874.
[23]	He Y, Fu L, Li Y, et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8(+) T cell immunity[J]. Cell Metab, 2021, 33: 988-1000.e7.
[24]	Hsiao YP, Chen HL, Tsai JN, et al. Administration of Lactobacillus reuteri Combined with Clostridium butyricum Attenuates Cisplatin-Induced Renal Damage by Gut Microbiota Reconstitution, Increasing Butyric Acid Production, and Suppressing Renal Inflammation[J]. Nutrients, 2021, 13:2792. .
[25]	García-González AP, Ritter AD, Shrestha S, et al. Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics[J]. Cell, 2017, 169: 431-441.e8.
[26]	Scott TA, Quintaneiro LM, Norvaisas P, et al. Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans[J]. Cell, 2017, 169: 442-456.e18.
[27]	Araki E, Ishikawa M, Iigo M, et al. Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11[J]. Jpn J Cancer Res, 1993, 84: 697-702.
[28]	Okuda H, Nishiyama T, Ogura K, et al. Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs[J]. Drug Metab Dispos, 1997, 25: 270-273.
[29]	Yan A, Culp E, Perry J, et al. Transformation of the Anticancer Drug Doxorubicin in the Human Gut Microbiome[J]. ACS Infect Dis, 2018, 4: 68-76.
[30]	Widemann B C, Schwartz S, Jayaprakash N, et al. Efficacy of glucarpidase (carboxypeptidase g2) in patients with acute kidney injury after high-dose methotrexate therapy[J]. Pharmacotherapy, 2014, 34: 427-439.
[31]	BTG International Inc.VORAXAZE9(Glucarpidase)for injection prescribing information[EB/OL].(2012-01-01)[2023-03-01].http://www.accesdate.fda.gov/drugsatfda_docs/label/2012/125327lbl.pdf.
[32]	Di Modica M, Gargari G, Regondi V, et al. Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer[J]. Cancer Res, 2021, 81: 2195-2206.
[33]	Chen YC, Chuang CH, Miao ZF, et al. Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer[J]. Front Oncol, 2022, 12: 955313.
[34]	Pal SK, Li SM, Wu X, et al. Stool Bacteriomic Profiling in Patients with Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitors[J]. Clin Cancer Res, 2015, 21: 5286-5293.
[35]	Zhao B, Zhou B, Dong C, et al. Lactobacillus reuteri Alleviates Gastrointestinal Toxicity of Rituximab by Regulating the Proinflammatory T Cells in vivo[J]. Front Microbiol, 2021, 12: 645500.
[36]	Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015, 350: 1079-1084.
[37]	Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science, 2015, 350: 1084-1089.
[38]	Kaesler S, Wölbing F, Kempf W E, et al. Targeting tumor-resident mast cells for effective anti-melanoma immune responses.[J]. JCI insight, 2019, 4: 125057.
[39]	Zhang SL, Han B, Mao YQ, et al. Lacticaseibacillus paracasei sh2020 induced antitumor immunity and synergized with anti-programmed cell death 1 to reduce tumor burden in mice.[J]. Gut microbes, 2022, 14: 2046246.
[40]	Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.[J]. Science, 2018, 359: 91-97.
[41]	Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to antiPD-1 immunotherapy in melanoma patients[J]. Science, 2018, 359: 97-103.
[42]	Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients[J]. Science, 2018, 359: 104-108.
[43]	Hamada K, Yoshimura K, Hirasawa Y, et al. Antibiotic Usage Reduced Overall Survival by over 70% in Non-small Cell Lung Cancer Patients on Anti-PD-1 Immunotherapy[J]. Anticancer Res, 2021, 41: 4985-4993.
[44]	Giordan Q, Salleron J, Vallance C, et al. Impact of Antibiotics and Proton Pump Inhibitors on Efficacy and Tolerance of Anti-PD-1 Immune Checkpoint Inhibitors[J]. Front Immunol, 2021, 12: 716317.
[45]	Oster P, Vaillant L, Riva E, et al. Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies[J]. Gut, 2022, 71: 457-466.
[46]	Che H, Xiong Q, Ma J, et al. Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors[J]. BMC cancer, 2022, 22: 904.
[47]	Chaput N, Lepage P, Coutzac C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab[J]. Ann Oncol, 2017, 28: 1368-1379.
[48]	Wang T, Zheng N, Luo Q, et al. Probiotics Lactobacillus reuteri Abrogates Immune Checkpoint Blockade-Associated Colitis by Inhibiting Group 3 Innate Lymphoid Cells[J]. Front Immunol, 2019, 10: 1235.
[49]	Wang F, Yin Q, Chen L, et al. Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade[J]. Proc Natl Acad Sci U S A, 2018, 115: 157-161.
[50]	Imai H, Saijo K, Komine K, et al. Antibiotic therapy augments the efficacy of gemcitabinecontaining regimens for advanced cancer: a retrospective study[J]. Cancer Manag Res, 2019, 11: 7953-7965.
[51]	Alimonti A, Satta F, Pavese I, et al. Prevention of irinotecan plus 5-fluorouracil/leucovorininduced diarrhoea by oral administration of neomycin plus bacitracin in first-line treatment of advanced colorectal cancer[J]. Ann Oncol, 2003, 14: 805-806.
[52]	Kuczma MP, Ding ZC, Li T, et al. The impact of antibiotic usage on the efficacy of chemoimmunotherapy is contingent on the source of tumor-reactive T cells[J]. Oncotarget, 2017, 8: 111931-111942.
[53]	Chang CW, Liu CY, Lee HC, et al. Lactobacillus casei Variety rhamnosus Probiotic Preventively Attenuates 5-Fluorouracil/Oxaliplatin-Induced Intestinal Injury in a Syngeneic Colorectal Cancer Model[J]. Front Microbiol, 2018, 9: 983.
[54]	Wu Y, Wu J, Lin Z, et al. Administration of a Probiotic Mixture Ameliorates CisplatinInduced Mucositis and Pica by Regulating 5-HT in Rats[J]. J Immunol Res, 2021, 2021: 9321196.
[55]	Han K, Nam J, Xu J, et al. Generation of systemic antitumour immunity via the in situ modulation of the gut microbiome by an orally administered inulin gel[J]. Nat Biomed Eng, 2021, 5: 1377-1388.
[56]	Yin L, Huang G, Khan I, et al. Poria cocos polysaccharides exert prebiotic function to attenuate the adverse effects and improve the therapeutic outcome of 5-FU in Apc(Min/+) mice[J]. Chin Med, 2022, 17: 116.
[57]	Andrade MER, Trindade LM, Leocádio PCL, et al. Association of Fructo-oligosaccharides and Arginine Improves Severity of Mucositis and Modulate the Intestinal Microbiota[J]. Probiotics Antimicrob Proteins, 2023,15:424-440. .
[58]	Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications[J]. Nat Rev Gastroenterol Hepatol, 2011, 9: 88-96.
[59]	Chang CW, Lee HC, Li LH, et al. Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer[J]. Int J Mol Sci, 2020, 21:386.
[60]	Davar D, Dzutsev A K, McCulloch J A, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients[J]. Science, 2021, 371: 595-602.
[61]	Borgers JSW, Burgers FH, Terveer EM, et al. Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial[J]. BMC cancer, 2022, 22: 1366.
[62]	Nakatsu G, Zhou H, Wu WKK, et al. Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes[J]. Gastroenterology, 2018, 155: 529-541.e5.
[63]	Coker OO, Nakatsu G, Dai RZ, et al. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer[J]. Gut, 2019, 68: 654-662.

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微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

doi: 10.12290/xhyxzz.2023-0212

通讯作者:
韩晓红,E-mail: hanxiaohong@pumch.cn

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Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug

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目录

留言板

微生物菌群与抗肿瘤药物疗效及不良反应相关性研究进展

doi: 10.12290/xhyxzz.2023-0212

通讯作者: 韩晓红,E-mail: hanxiaohong@pumch.cn

计量

出版历程

Research Progress on the Correlation Between Microbiota and the Efficacy and Adverse Reactions of Antitumor Drug

计量

出版历程

目录

通讯作者:
韩晓红,E-mail: hanxiaohong@pumch.cn