Current progress in systemic therapy for biliary tract cancers

Abstract

Background Biliary tract cancers (BTCs) are heterogeneous cancers that include cancers of the bile duct and gallbladder. Although they are relatively uncommon, most patients with BTC are diagnosed at advanced‐stage disease with high mortality rates. Recently, systemic therapy options for patients with BTC have evolved. This paper reviews recent advancements in systemic therapy and the results of key clinical trials in BTC. Methods A literature search in PubMed and Google Scholar was performed using keywords related to BTC and systemic therapy. Studies that were presented in major international cancer research conferences were also included. Results The evidence shows that adjuvant capecitabine has been associated with a lower relapse rate in early‐stage BTC. In unselected patients with advanced BTC, combination chemotherapy is a standard treatment option. However, with a better understanding of the molecular profile of BTC, there has been a shift toward targeted agents in BTC that have shown promising responses. The evolving data also support the evolving role of immunotherapy in patients with deficient DNA mismatch repair or PD‐L1‐positive BTC. Discussion Systemic treatment options for BTC have improved. The future identification of new targets, novel compounds, and predictive markers is a key step toward the use of personalized medicine in BTC.

Patient‐derived organoids for personalized gallbladder cancer modelling and drug screening

“…However, in many patients with this highly heterogeneous tumour, the therapeutic response is not satisfactory. There is an urgent need to develop more personalized and targeted therapies 4–6 . One of the major barriers to the development of novel treatments is the lack of appropriate models that can accurately recapitulate the histological complexity and genetic heterogeneity of human cancers.…”

Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice

“…In BTC, up to 25% cases were found to have DDR defects. 8,26 In the DDR network, ataxia-telangiectasia-mutated (ATM) and ataxia-telangiectasia-Rad3-related (ATR) enzymes, the essential non-redundant DNA damage sensors, play critical roles in the DSBs, SSBs, and DNA repair. 27 ATM is generally recruited after DSBs occur, while ATR recognizes the regions of replication protein Acoated single-strand DNA to maintain genomic integrity in S or G2/M phase of the cell cycle.…”

“…DNA damage repair (DDR) is a multicomplex network event involving multiple signaling pathways, and the decreased level of DDR has been identified in different cancers. In BTC, up to 25% cases were found to have DDR defects 8,26 …”

Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance

“…This therapeutic approach can be especially advantageous in the case of CCA, since this is one of the tumors with the highest number of genetic alterations that are potentially druggable, which means they affect gene-encoding proteins that can be targeted directly or indirectly with approved or investigational drugs [36]. Several recent studies have described the current status of targeted therapies in clinical development in BTCs [2,[37][38][39][40][41]. However, none of them have focused on information related to MPRs.…”