Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications

Hendrien Kuipers*, Tessa J J de Bitter, Marieke T de Boer, Rachel S van der Post, Maarten W Nijkamp, Philip R de Reuver, Rudolf S N Fehrmann, Frederik J H Hoogwater*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

7 Citations (Scopus)
15 Downloads (Pure)

Abstract

Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search was performed utilizing PubMed, EMBASE, Cochrane Library, and Web of Science. Only studies reporting genetic alterations in human GBC were included. In total, data were extracted from 62 articles, describing a total of 3893 GBC samples. Frequently detected genetic alterations (>5% in >5 samples across all studies) in GBC for which targeted therapies are available in other cancer types included mutations in ATM, ERBB2, and PIK3CA, and ERBB2 amplifications. High tumor mutational burden (TMB-H) and microsatellite instability (MSI-H) were infrequently observed in GBC (1.7% and 3.5%, respectively). For solid cancers with TMB-H or MSI-H pembrolizumab is FDA-approved and shows an objective response rates of 50% for TMB-H GBC and 41% for MSI-H biliary tract cancer. Only nine clinical trials evaluated targeted therapies in GBC directed at frequently altered genes (ERBB2, ARID1A, ATM, and KRAS). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials.

Original languageEnglish
Article number5257
Number of pages20
JournalCancers
Volume13
Issue number21
DOIs
Publication statusPublished - 20-Oct-2021

Keywords

  • gallbladder cancer
  • gene mutations
  • genetic alterations
  • tumor mutational burden
  • microsatellite instability
  • targeted therapy
  • TUMOR MUTATIONAL BURDEN
  • LAPATINIB PLUS CAPECITABINE
  • BILIARY-TRACT CARCINOMAS
  • GROWTH-FACTOR RECEPTOR
  • K-RAS ONCOGENE
  • MICROSATELLITE INSTABILITY
  • OPEN-LABEL
  • GENOMIC ALTERATIONS
  • SOMATIC MUTATIONS
  • TRASTUZUMAB

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