胆管癌靶向治疗的研究现状

邓海敏; 段华新

doi:10.3969/j.issn.1001-5256.2020.12.046

胆管癌靶向治疗的研究现状

DOI: 10.3969/j.issn.1001-5256.2020.12.046

湖南师范大学附属第一医院/湖南省人民医院肿瘤科

基金项目:

湖南省自然科学基金项目（2020JJ8084）；

详细信息

中图分类号: R735.8
计量
- 文章访问数: 553
- HTML全文浏览量: 19
- PDF下载量: 105
- 被引次数: 0
出版历程
- 收稿日期: 2020-05-25
- 出版日期: 2020-12-20

Current status of the research on targeted therapy for cholangiocarcinoma

Department of Oncology,The First Affiliated Hospital of Hunan Normal University & Hunan Provincial People's Hospital

Research funding:

摘要

摘要:
胆管癌是指来源于胆管上皮的恶性肿瘤,虽发病率低,但因其发病时无突出的临床表现,发现时多为终末期。目前面临治疗手段不足、预后不佳、生存率低等问题,所以迫切需要找到新的治疗方式来突破胆管癌治疗的瓶颈。随着对胆管癌基因图谱表达研究的深入和下一代基因测序技术的发展,已经发现了一些潜在的靶点,如FGFR、IDH1/2等,使靶向治疗胆管癌成为一种可行的治疗手段。靶向治疗是指通过干扰肿瘤细胞生长涉及的特异性分子来阻断肿瘤细胞的生长,具有特异性高、毒性低、疗效可观等优点。近来,靶向治疗已经逐渐成为胆管癌治疗的研究热点,阐述了胆管癌靶向治疗的现状和面临的问题。
- 胆管肿瘤 /
- 分子靶向治疗 /
- 治疗学
Abstract:
Cholangiocarcinoma is a malignant tumor originating from the epithelium of bile ducts,and although it has a low incidence rate,most patients are in the end stage at the time of diagnosis since there are no prominent clinical manifestations at disease onset. Since there are problems such as insufficient treatment options,poor prognosis,and low survival rates,it is urgent to find new treatment methods to make breakthroughs in the treatment of cholangiocarcinoma. With the in-depth studies on cholangiocarcinoma gene mapping and the development of next-generation sequencing technologies,a number of potential targets have been discovered,such as FGFR and IDH1/2,making targeted therapy for cholangiocarcinoma a feasible treatment option. Targeted therapy is a treatment modality that blocks the growth of tumor cells by interfering with the specific molecules involved in tumor cell growth,with the advantages of high specificity,low toxicity,and considerable therapeutic effect. In recent years,targeted therapy has become a research hotspot in the treatment of cholangiocarcinoma. This article elaborates on the current status and challenges in targeted therapy for cholangiocarcinoma.
- bile duct neoplasms /
- molecular targeted therapy /
- therapeutics

HTML全文

参考文献(43)

[1] RIZVI S,KHAN SA,HALLEMEIER CL,et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol,2018,15(2):95-111.

[2] WANG X,LI XC. Progress in palliative care of bile duct cancer[J]. J Clin Hepatol,2016,32(5):1022-1025.(in Chinese)王荇，李相成．胆管癌姑息治疗的研究进展[J]．临床肝胆病杂志，2016,32(5):1022-1025.

[3] CILLO U,FONDEVILA C,DONADON M,et al. Surgery for cholangiocarcinoma[J]. Liver Int,2019,39(Suppl 1):143-155.

[4] VALLE J,WASAN H,PALMER DH,et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med,2010,362(14):1273-1281.

[5] KATOH M. Fibroblast growth factor receptors as treatment targets in clinical oncology[J]. Nat Rev Clin Oncol,2019,16(2):105-122.

[6] SIA D,LOSIC B,MOEINI A,et al. Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma[J]. Nat Commun,2015,6:6087.

[7] JAVLE M,LOWERY M,SHROFF RT,et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma[J]. J Clin Oncol,2018,36(3):276-282.

[8] GOYAL L,ARKENAU HT,TRAN B,et al. Early clinical efficacy of TAS-120,a covalently bound FGFR inhibitor,in patients with cholangiocarcinoma[J]. Ann Oncol,2017,28(Suppl3):iii137-iii149.

[9] KROOK MA,LENYO A,WILBERDING M,et al. Efficacy of FGFR Inhibitors and combination therapies for acquired resistance in FGFR2-fusion cholangiocarcinoma[J]. Mol Cancer Ther,2020,19(3):847-857.

[10] ABOU-ALFA GK,SAHAI V,HOLLEBECQUE A,et al. Pemigatinib for previously treated,locally advanced or metastatic cholangiocarcinoma:A multicentre, open-label, phase 2study[J]. Lancet Oncol,2020,21(5):671-684.

[11] WAITKUS MS,DIPLAS BH,YAN H. Biological role and therapeutic potential of IDH mutations in cancer[J]. Cancer Cell,2018,34(2):186-195.

[12] DANG L,YEN K,ATTAR EC. IDH mutations in cancer and progress toward development of targeted therapeutics[J].Ann Oncol,2016,27(4):599-608.

[13] BORGER DR,TANABE KK,FAN KC,et al. Frequent mutation of isocitrate dehydrogenase(IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping[J]. Oncologist,2012,17(1):72-79.

[14] POPOVICI-MULLER J,LEMIEUX RM,ARTIN E,et al. Discovery of AG-120(Ivosidenib):A first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers[J].ACS Med Chem Lett,2018,9(4):300-305.

[15] ABOU-ALFA GK,MACARULLA T,JAVLE MM,et al. Ivosidenib in IDH1-mutant,chem otherapy-refractory cholangiocarcinoma(Clar IDHy):A multicentre,randomised,doubleblind,placebo-controlled,phase 3 study[J]. Lancet Oncol,2020,21(6):796-807.

[16] YOSHIKAWA D,OJIMA H,IWASAKI M,et al. Clinicopathological and prognostic sig nificance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma[J]. Br J Cancer,2008,98(2):418-425.

[17] XU J,LIU X,YANG S,et al. Clinical response to apatinib monotherapy in advanced non-small cell lung cancer[J]. Asia Pac J Clin Oncol,2018,14(3):264-269.

[18] LI CM,LIU ZC,BAO YT,et al. Extraordinary response of metastatic pancreatic cancer to apatinib after failed chemotherapy:A case report and literature review[J]. World J Gastroenterol,2017,23(41):7478-7488.

[19] LU W,KE H,QIANSHAN D,et al. Apatinib has anti-tumor effects and induces autophagy in colon cancer cells[J]. Iran J Basic Med Sci,2017,20(9):990-995.

[20] PENG H,ZHANG Q,LI J,et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma[J]. Oncotarget,2016,7(13):17220-17229.

[21] WANG LY,GONG S,GAO LP,et al. Apatinib for treating advanced intrahepatic cholangiocarcinoma after failed chemotherapy:A case report and literature review[J]. Medicine(Baltimore),2018,97(49):e13372.

[22] VALLE JW,WASAN H,LOPES A,et al. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer(ABC-03):A randomised phase 2 trial[J]. Lancet Oncol,2015,16(8):967-978.

[23] IYER RV,POKURI VK,GROMAN A,et al. A multicenter phase IIstudy of gemcitabine,cape citabine,and bevacizumab for locally advanced or metastatic biliary tract cancer[J].Am J Clin Oncol,2018,41(7):649-655.

[24] WALTER D,HARTMANN S,WAIDMANN O. Update on cholangiocarcinoma:Potential impact of genomic studies on clinical management[J]. Z Gastroenterol,2017,5(6):575-581.

[25] SCHADENDORF D,van AKKOOI ACJ,BERKING C,et al.Melanoma[J]. Lancet,2018,392(10151):971-984.

[26] O’LEARY CG,ANDELKOVIC V,LADWA R,et al. Targeting BRAF mutations in nonsmall cell lung cancer[J]. Transl Lung Cancer Res,2019,8(6):1119-1124.

[27] SILKIN SV,STARTSEV SS,KRASNOVA ME,et al. Complete clinical response of BRAF-mutated cholangiocarcinoma to vemurafenib,panitumumab,and irinotecan[J]. J Gastrointest Cancer,2016,47(4):502-505.

[28] RAVAUD A,MOTZER RJ,PANDHA HS,et al. Adjuvant sunitinib in high-risk renacell carcinoma after nephrectomy[J]. N Engl J Med,2016,375(23):2246-2254.

[29] DEMETRI GD,van OOSTEROM AT,GARRETT CR,et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib:A randomised controlled trial[J]. Lancet,2006,368(9544):1329-1338.

[30] LI X,GAO L,ZHANG L,et al. Third-line sunitinib treatment in a VHL-mutated metastatic intrahepatic cholangiocarcinoma:A case report and literature review[J]. Cancer Biol Ther,2020.(Online ahead of print)

[31] PELLAT A,VAQUERO J,FOUASSIER L. Role of ErbB/HER family of receptor tyrosine kinases in cholangiocyte biology[J]. Hepatology,2018,67(2):762-773.

[32] CHURI CR,SHROFF R,WANG Y,et al. Mutation profiling in cholangiocarcinoma:Prognostic and therapeutic implications[J]. PLo S One,2014,9(12):e115383.

[33] GALDY S,LAMARCA A,MCNAMARA MG,et al. HER2/HER3pathway in biliary tract malignancies; systematic review and meta-analysis:A potential therapeutic target?[J]. Cancer Metastasis Rev,2017,36(1):141-157.

[34] YOO KH,KIM NK,KWON WI,et al. Genomic alterations in biliary tract cancer using targeted sequencing[J]. Transl Oncol,2016,9(3):173-178.

[35] NAM AR,KIM JW,CHA Y,et al. Therapeutic implication of HER2 in advanced biliary tract cancer[J]. Oncotarget,2016,7(36):58007-58021.

[36] KAWAMOTO T,ISHIGE K,THOMAS M,et al. Overexpression and gene amplification of EGFR,HER2,and HER3 in biliary tract carcinomas,and the possibility for therapy with the HER2-targeting antibody pertuzumab[J]. J Gastroenterol,2015,50(4):467-479.

[37] LEE J,PARK SH,CHANG HM,et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer:A multicenter,open-label,randomised,phase 3 study[J]. Lancet Oncol,2012,13(2):181-188.

[38] RIZZO A,FREGA G,RICCI AD,et al. Anti-EGFR monoclonal antibodies in advanced biliary tract cancer:A systematic review and Meta-analysis[J]. In Vivo,2020,34(2):479-488.

[39] JANG SI,FANG S,BAEK YY,et al. Local delivery of gemcitabine inhibits pancreatic and cholangiocarcinoma tumor growth by promoting epidermal growth factor receptor degradation[J]. Int J Mol Sci,2020,21(5):1605.

[40] BRIDGEWATER J,LOPES A,BEARE S,et al. A phase 1b study of selumetinib in combination with cisplatin and gemcitabine in advanced or metastatic biliary tract cancer:The ABC-04 study[J]. BMC Cancer,2016,16:2153-2174.

[41] KIM JW,LEE KH,KIM JW,et al. Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway:Phase Ib study[J]. Br J Cancer,2019,121(4):332-339.

[42] RIZVI S,GORES GJ. Emerging molecular therapeutic targets for cholangiocarcinoma[J]. J Hepatol,2017,67(3):632-644.

[43] DING Q,ZHANG Z,LIU JJ,et al. Discovery of RG7388,a potent and selective p53-MDM2 inhibitor in clinical development[J]. J Med Chem,2013,56(14):5979-5983.

施引文献

资源附件(0)

访问统计