中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 9
Sep.  2023
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Article Contents

Systemic therapy for gallbladder cancer in the era of precision medicine: Coexistence of opportunities and challenges

DOI: 10.3969/j.issn.1001-5256.2023.09.005
Research funding:

National Natural Science Foundation of China (62076194);

Key Research and Development Plan of Shaanxi Province (2022SF-606);

Key Research and Development Plan of Shaanxi Province (2022-YBSF-441)

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  • Corresponding author: GENG Zhimin, gengzhimin@mail.xjtu.edu.cn (ORCID: 0000-0003-2645-9808)
  • Received Date: 2023-06-12
  • Accepted Date: 2023-07-15
  • Published Date: 2023-09-19
  • Gallbladder cancer is the most common malignant tumor of the biliary system, and its treatment outcome is greatly limited by its invasiveness and insensitivity to conventional radiotherapy and chemotherapy. In recent years, the emergence of various high-throughput sequencing techniques has helped to deepen the understanding of the molecular mechanisms of gallbladder cancer, and promising therapeutic targets have been identified and studied in clinical trials at present. A comprehensive exploration of the molecular subtypes of gallbladder cancer is of great importance for developing individualized diagnosis and treatment strategies. Several molecular subtyping systems have been proposed based on multi-omics features, which enhances the comprehension of the molecular mechanisms and features of gallbladder cancer among clinical researchers. With reference to the latest research advances in gallbladder cancer, this article investigates the challenges in the mutation targets and molecular subtyping of gallbladder cancer, analyzes the novel targets for targeted therapy and immunotherapy, and proposes new ideas for the precise diagnosis and individualized treatment of gallbladder cancer.

     

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  • [1]
    ROA JC, GARCÍA P, KAPOOR VK, et al. Gallbladder cancer[J]. Nat Rev Dis Primers, 2022, 8( 1): 69. DOI: 10.1038/s41572-022-00398-y.
    [2]
    ARE C, AHMAD H, RAVIPATI A, et al. Global epidemiological trends and variations in the burden of gallbladder cancer[J]. J Surg Oncol, 2017, 115( 5): 580- 590. DOI: 10.1002/jso.24546.
    [3]
    OKADA K, KIJIMA H, IMAIZUMI T, et al. Wall-invasion pattern correlates with survival of patients with gallbladder adenocarcinoma[J]. Anticancer Res, 2009, 29( 2): 685- 691.
    [4]
    SHIMIZU Y, ASHIDA R, SUGIURA T, et al. ASO visual abstract: early recurrence in resected gallbladder carcinoma-clinical impact and its preoperative predictive score[J]. Ann Surg Oncol, 2022, 29( 9): 5460- 5461. DOI: 10.1245/s10434-022-12018-w.
    [5]
    SAHARA K, TSILIMIGRAS DI, KIKUCHI Y, et al. Defining and predicting early recurrence after resection for gallbladder cancer[J]. Ann Surg Oncol, 2021, 28( 1): 417- 425. DOI: 10.1245/s10434-020-09108-y.
    [6]
    YANG P, JAVLE M, PANG F, et al. Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients[J]. Hepatobiliary Surg Nutr, 2019, 8( 6): 604- 614. DOI: 10.21037/hbsn.2019.04.11.
    [7]
    YU C, ZHANG H, LUO J, et al. Abstract 2194: Comparison of molecular profiling between Chinese cholangiocarcinoma and gallbladder cancer through next-generation sequencing[J]. Cancer Res, 2021, 81( 13_Suppl): 2194. DOI: 10.1158/1538-7445.AM2021-2194.
    [8]
    CHEN X, PANG J, LIU C, et al. Genomic characterization of chinese biliary tract cancers identifies differences between subtypes and therapeutic biomarkers[J]. Cancer Res, 2022, 82( 12_Suppl): 5765.
    [9]
    MEHROTRA R, TULSYAN S, HUSSAIN S, et al. Genetic landscape of gallbladder cancer: Global overview[J]. Mutat Res Rev Mutat Res, 2018, 778: 61- 71. DOI: 10.1016/j.mrrev.2018.08.003.
    [10]
    NEPAL C, ZHU B, O’ROURKE CJ, et al. Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes[J]. J Hepatol, 2021, 74( 5): 1132- 1144. DOI: 10.1016/j.jhep.2020.11.033.
    [11]
    PANDEY A, STAWISKI EW, DURINCK S, et al. Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate[J]. Nat Commun, 2020, 11( 1): 4225. DOI: 10.1038/s41467-020-17880-4.
    [12]
    ALEXANDROV LB, KIM J, HARADHVALA NJ, et al. The repertoire of mutational signatures in human cancer[J]. Nature, 2020, 578( 7793): 94- 101. DOI: 10.1038/s41586-020-1943-3.
    [13]
    NAKAMURA H, ARAI Y, TOTOKI Y, et al. Genomic spectra of biliary tract cancer[J]. Nat Genet, 2015, 47( 9): 1003- 1010. DOI: 10.1038/ng.3375.
    [14]
    LI M, ZHANG Z, LI X, et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway[J]. Nat Genet, 2014, 46( 8): 872- 876. DOI: 10.1038/ng.3030.
    [15]
    LI M, LIU F, ZHANG F, et al. Genomic ERBB2/ERBB3 mutations promote PD-L1-mediated immune escape in gallbladder cancer: a whole-exome sequencing analysis[J]. Gut, 2019, 68( 6): 1024- 1033. DOI: 10.1136/gutjnl-2018-316039.
    [16]
    JAVLE M, RASHID A, CHURI C, et al. Molecular characterization of gallbladder cancer using somatic mutation profiling[J]. Hum Pathol, 2014, 45( 4): 701- 708. DOI: 10.1016/j.humpath.2013.11.001.
    [17]
    ABDEL-WAHAB R, YAP TA, MADISON R, et al. Genomic profiling reveals high frequency of DNA repair genetic aberrations in gallbladder cancer[J]. Sci Rep, 2020, 10( 1): 22087. DOI: 10.1038/s41598-020-77939-6.
    [18]
    XIE F, XU X, XU A, et al. Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and gallbladder carcinoma[J]. Hum Pathol, 2014, 45( 3): 513- 521. DOI: 10.1016/j.humpath.2013.10.017.
    [19]
    JAVLE MM, CATENACCI D, JAIN A, et al. Precision medicine for gallbladder cancer using somatic copy number amplifications(SCNA) and DNA repair pathway gene alterations[J]. J Clin Oncol, 2017, 35( 15_Suppl): 4076. DOI: 10.1200/JCO.2017.35.15_suppl.4076.
    [20]
    ROA I, DE TORO G, SCHALPER K, et al. Overexpression of the HER2/neu gene: A new therapeutic possibility for patients with advanced gallbladder cancer[J]. Gastrointest Cancer Res, 2014, 7( 2): 42- 48.
    [21]
    ZHANG Y, ZUO C, LIU L, et al. Single-cell RNA-sequencing atlas reveals an MDK-dependent immunosuppressive environment in ErbB pathway-mutated gallbladder cancer[J]. J Hepatol, 2021, 75( 5): 1128- 1141. DOI: 10.1016/j.jhep.2021.06.023.
    [22]
    IYER P, SHRIKHANDE SV, RANJAN M, et al. ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer[J]. Int J Cancer, 2019, 144( 8): 2008- 2019. DOI: 10.1002/ijc.31916.
    [23]
    GOEPPERT B, ROESSLER S, RENNER M, et al. Low frequency of mismatch repair deficiency in gallbladder cancer[J]. Diagn Pathol, 2019, 14( 1): 36. DOI: 10.1186/s13000-019-0813-5.
    [24]
    de BITTER T, de REUVER PR, de SAVORNIN LOHMAN E, et al. Comprehensive clinicopathological and genomic profiling of gallbladder cancer reveals actionable targets in half of patients[J]. NPJ Precis Oncol, 2022, 6( 1): 83. DOI: 10.1038/s41698-022-00327-y.
    [25]
    BIZAMA C, GARCÍA P, ESPINOZA JA, et al. Targeting specific molecular pathways holds promise for advanced gallbladder cancer therapy[J]. Cancer Treat Rev, 2015, 41( 3): 222- 234. DOI: 10.1016/j.ctrv.2015.01.003.
    [26]
    MISHRA S, KUMARI S, SRIVASTAVA P, et al. Genomic profiling of gallbladder carcinoma: Targetable mutations and pathways involved[J]. Pathol Res Pract, 2022, 232: 153806. DOI: 10.1016/j.prp.2022.153806.
    [27]
    EBATA N, FUJITA M, SASAGAWA S, et al. Molecular classification and tumor microenvironment characterization of gallbladder cancer by comprehensive genomic and transcriptomic analysis[J]. Cancers(Basel), 2021, 13( 4): 733. DOI: 10.3390/cancers13040733.
    [28]
    AGGARWAL V, MONTOYA CA, DONNENBERG VS, et al. Interplay between tumor microenvironment and partial EMT as the driver of tumor progression[J]. iScience, 2021, 24( 2): 102113. DOI: 10.1016/j.isci.2021.102113.
    [29]
    ROMEO E, CASERTA CA, RUMIO C, et al. The vicious cross-talk between tumor cells with an EMT phenotype and cells of the immune system[J]. Cells, 2019, 8( 5): 460. DOI: 10.3390/cells8050460.
    [30]
    CHEN P, WANG Y, LI J, et al. Diversity and intratumoral heterogeneity in human gallbladder cancer progression revealed by single-cell RNA sequencing[J]. Clin Transl Med, 2021, 11( 6): e462. DOI: 10.1002/ctm2.462.
    [31]
    JAVLE M, BORAD MJ, AZAD NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer(MyPathway): a multicentre, open-label, phase 2a, multiple basket study[J]. Lancet Oncol, 2021, 22( 9): 1290- 1300. DOI: 10.1016/S1470-2045(21)00336-3.
    [32]
    MERIC-BERNSTAMF, HANNADL, EL-KHOUEIRYAB, et al. Zanidatamab(ZW25) in HER2-positive biliary tract cancers(BTCs): results from a phase I study[J]. J Clin Oncol, 2021, 39( 3_suppl): 299. DOI: 10.1200/JCO.2021.39.3_suppl.299.
    [33]
    HARDING JJ, FAN J, OH DY, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer(HERIZON-BTC-01): a multicentre, single-arm, phase 2b study[J]. Lancet Oncol, 2023, 24( 7): 772- 782. DOI: 10.1016/S1470-2045(23)00242-5.
    [34]
    JAVLE M, ZHAO H, ABOU-ALFA GK. Systemic therapy for gallbladder cancer[J]. Chin Clin Oncol, 2019, 8( 4): 44. DOI: 10.21037/cco.2019.08.14.
    [35]
    OHBA A, MORIZANE C, UENO M, et al. Multicenter phase II trial of trastuzumab deruxtecan for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial[J]. Future Oncol, 2022, 18( 19): 2351- 2360. DOI: 10.2217/fon-2022-0214.
    [36]
    Biliary Tract Tumor Committee of China Anti Cancer Association. China Anti Cancer Association guidelines for targeted therapy and immunotherapy of biliary tract malignancies(2022)(summary edition)[J]. Chin J Pract Surg, 2023, 43( 5): 481- 491. DOI: 10.19538/j.cjps.issn1005-2208.2023.05.01.

    中国抗癌协会胆道肿瘤专业委员会. 中国抗癌协会胆道恶性肿瘤靶向及免疫治疗指南(2022)(简要版)[J]. 中国实用外科杂志, 2023, 43( 5): 481- 491. DOI: 10.19538/j.cjps.issn1005-2208.2023.05.01.
    [37]
    HARDING J, PIHA-PAUL S, SHAH RH, et al. Targeting HER2 mutation–positive advanced biliary tract cancers with neratinib: Final results from the phase 2 SUMMIT basket trial[J]. J Clin Oncol, 2022, 40( Suppl 16): 4079.
    [38]
    JAVLE MM, OH DY, IKEDA M, et al. Varlitinib plus capecitabine in second-line advanced biliary tract cancer: A randomized, phase II study(TreeTopp)[J]. ESMO Open, 2022, 7( 1): 100314. DOI: 10.1016/j.esmoop.2021.100314.
    [39]
    MALKA D, CERVERA P, FOULON S, et al. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer(BINGO): A randomised, open-label, non-comparative phase 2 trial[J]. Lancet Oncol, 2014, 15( 8): 819- 828. DOI: 10.1016/S1470-2045(14)70212-8.
    [40]
    DEMOLS A, BORBATH I, van den EYNDE M, et al. Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial[J]. Ann Oncol, 2020, 31( 9): 1169- 1177. DOI: 10.1016/j.annonc.2020.05.018.
    [41]
    LEE J, PARK SH, CHANG HM, et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: A multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol, 2012, 13( 2): 181- 188. DOI: 10.1016/S1470-2045(11)70301-1.
    [42]
    LOWERY MA, BRADLEY M, CHOU JF, et al. Binimetinib plus gemcitabine and cisplatin phase I/II trial in patients with advanced biliary cancers[J]. Clin Cancer Res, 2019, 25( 3): 937- 945. DOI: 10.1158/1078-0432.CCR-18-1927.
    [43]
    LEE S, SHROFF RT, MAKAWITA S, et al. Phase II study of ramucirumab in advanced biliary tract cancer previously treated by gemcitabine-based chemotherapy[J]. Clin Cancer Res, 2022, 28( 11): 2229- 2236. DOI: 10.1158/1078-0432.CCR-21-3548.
    [44]
    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. DOI: 10.1016/S1470-2045(15)00139-4.
    [45]
    SONG X, HU Y, LI Y, et al. Overview of current targeted therapy in gallbladder cancer[J]. Signal Transduct Target Ther, 2020, 5( 1): 230. DOI: 10.1038/s41392-020-00324-2.
    [46]
    PIHA-PAUL SA, OH DY, UENO M, et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies[J]. Int J Cancer, 2020, 147( 8): 2190- 2198. DOI: 10.1002/ijc.33013.
    [47]
    KIM RD, CHUNG V, ALESE OB, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer[J]. JAMA Oncol, 2020, 6( 6): 888- 894. DOI: 10.1001/jamaoncol.2020.0930.
    [48]
    KELLEY RK, MITCHELL E, BEHR S, et al. Phase II trial of pembrolizumab(PEM) plus granulocyte macrophage colony stimulating factor(GM-CSF) in advanced biliary cancers(ABC)[J]. J Clin Oncol, 2018, 36( Suppl 4): 386.
    [49]
    KLEIN O, KEE D, NAGRIAL A, et al. Evaluation of combination nivolumab and ipilimumab immunotherapy in patients with advanced biliary tract cancers: Subgroup analysis of a phase 2 nonrandomized clinical trial[J]. JAMA Oncol, 2020, 6( 9): 1405- 1409. DOI: 10.1001/jamaoncol.2020.2814.
    [50]
    UENO M, IKEDA M, MORIZANE C, et al. Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: A non-randomised, multicentre, open-label, phase 1 study[J]. Lancet Gastroenterol Hepatol, 2019, 4( 8): 611- 621. DOI: 10.1016/S2468-1253(19)30086-X.
    [51]
    DOKI Y, UENO M, HSU CH, et al. Tolerability and efficacy of durvalumab, either as monotherapy or in combination with tremelimumab, in patients from Asia with advanced biliary tract, esophageal, or head-and-neck cancer[J]. Cancer Med, 2022, 11( 13): 2550- 2560. DOI: 10.1002/cam4.4593.
    [52]
    OH DY, RUTH HE A, QIN SK, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer[J]. NEJM Evid, 2022, 1( 8): a2200015. DOI: 10.1056/evidoa2200015.
    [53]
    KELLEY RK, UENO M, YOO C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer(KEYNOTE-966): A randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2023, 401( 10391): 1853- 1865. DOI: 10.1016/S0140-6736(23)00727-4.
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