Current and emerging immunotherapeutic approaches for biliary tract cancers

Biliary tract cancers (BTCs) comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses. The benefit of chemotherapy seems to have reached a bottleneck and, therefore, new effective therapeutic strategies for advanced BTCs are needed. Molecularly targeted therapies in selec...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Hepatobiliary & pancreatic diseases international 2022-10, Vol.21 (5), p.440-449
Hauptverfasser: Yuan, Zhen-Gang, Zeng, Tian-Mei, Tao, Chen-Jie
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Biliary tract cancers (BTCs) comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses. The benefit of chemotherapy seems to have reached a bottleneck and, therefore, new effective therapeutic strategies for advanced BTCs are needed. Molecularly targeted therapies in selected patients are rapidly changing the situation. However, the low frequency of specific driver alterations in BTCs limits their wide application. Recently, immunotherapeutic approaches are also under active investigation in BTCs, but the role of immunotherapy in BTCs remains controversial. PubMed, Web of Science, and meeting resources were searched for relevant articles published from January 2017 to May 2022. The search aimed to identify current and emerging immunotherapeutic approaches for BTCs. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/. Immunotherapy in BTC patients is currently under investigation, and most of the investigations focused on the application of immune checkpoint inhibitors (ICIs). However, only a subgroup of BTCs with microsatellite-instability high (MSI-H)/DNA mismatch repair-deficient (dMMR) or tumor mutational burden-high (TMB-H) benefit from monotherapy of ICIs, and limited activity was observed in the second or subsequent settings. Nevertheless, promising results come from studies of ICIs in combination with other therapeutic approaches, including chemotherapy, in advanced BTCs, with a moderate toxicity profile. Recent studies demonstrated that compared to GEMCIS alone, durvalumab plus GEMCIS significantly improved patient survival (TOPAZ-1 trial) and that ICIs-combined chemoimmunotherapy is poised to become a new frontline therapy option, regardless of TMB and MMR/MSI status. Adoptive cell therapy and peptide- or dendritic-based cancer vaccines are other immunotherapeutic options that are being studied in BTCs. Numerous biomarkers have been investigated to define their predictive role in response to ICIs, but no predictive biomarker has been validated, except MSI-H/dMMR. The role of immunotherapy in BTCs is currently under investigation and the results of ongoing studies are eagerly anticipated. Several studies have demonstrated the safety and efficacy of ICIs in combination with chemotherapy in treatment-naive patients, such as the phase III TOPAZ-1 trial, which will change the standard care of first-line chemotherapy for advanced BTCs. However, further research is needed t
ISSN:1499-3872
DOI:10.1016/j.hbpd.2022.08.015