Cholangiocarcinoma: what are the options in all comers and how has the advent of molecular profiling opened the way to personalised medicine ?

Roth, Gaël S.; Neuzillet, Cindy; Sarabi, Matthieu; Edeline, Julien; Malka, David; Lièvre, Astrid

doi:10.1016/j.ejca.2022.11.006

Cited by 18 publications

(19 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first‐line therapy for CCA consists of a combination of cisplatin and gemcitabine chemotherapy, which only slightly slows down tumour progression. Moreover, most patients experience chemotherapy resistance 2,35 . The frequent failure of chemotherapy prompted research into tumour genomics and the identification of targeted therapies 36 .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, CCA is obscured by the liver and stomach, therefore confounding its diagnosis via detection or biopsy 5 . CCA is fatal cancer with a 5‐year overall survival (OS) rate of <5% and its incidence is increasing worldwide 2 . Although surgical resection is an effective treatment for CCA, approximately 60%–70% of patients are diagnosed at an already advanced stage and are ineligible for surgical resection 5–7 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Degradation of AZGP1 suppresses apoptosis and facilitates cholangiocarcinoma tumorigenesis via TRIM25

Yun,

Jeong,

Kim

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

Alpha‐2‐Glycoprotein 1, Zinc‐binding (AZGP1, ZAG) is a secreted protein that is synthesized by adipocytes and epithelial cells; it is downregulated in several malignancies such as breast, prostate, liver and lung cancers. However, its function remains unclear in cholangiocarcinoma (CCA). Here, we evaluated the impact AZGP1 in CCA using Gene Expression Omnibus (GEO) and GEPIA. In addition, we analysed AZGP1 expression using quantitative reverse transcription PCR and western blotting. Expression of AZGP1 was nearly deficient in CCA patients and cell lines and was associated with poor prognosis. AZGP1 overexpression upregulated apoptosis markers. Co‐immunoprecipitation experiments showed that AZGP1 interacts with tripartite motif‐containing protein 25 (TRIM25), and tissue microarray and bioinformatic analysis showed that AZGP1 is negatively correlated with TRIM25 expression in CCA. Thereafter, TRIM25 knockdown led to AZGP1 upregulation and induced cancer cell apoptosis. TRIM25 targets AZGP1 for degradation by catalysing its ubiquitination. AZGP1 overexpression significantly suppressed tumour growth in a xenograft mouse model. This study findings suggest that AZGP1 is a potential therapeutic target or a diagnostic biomarker for treating patients with CCA.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Degradation of AZGP1 suppresses apoptosis and facilitates cholangiocarcinoma tumorigenesis via TRIM25

Yun,

Jeong,

Kim

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Cholangiocarcinoma (CCA) is major type of biliary tract cancer (BTC) that originates from the bile duct epithelium (1). It is the second most common hepatobiliary cancer with high malignancy and poor prognosis (1). Depending on its anatomical location, CCA is divided into extrahepatic cholangiocarcinoma (ECC) and intrahepatic cholangiocarcinoma (ICC).…”

Section: Introductionmentioning

confidence: 99%

Immune-related adverse events correlate with the efficacy of PD-1 inhibitors combination therapy in advanced cholangiocarcinoma patients: A retrospective cohort study

Zhang

Wang

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundWhether irAEs can predict the efficacy of PD-1 inhibitors in cholangiocarcinoma (CCA) has not been assessed. Therefore, this study aims to investigate the correlation between irAEs and the therapeutic effect of PD-1 inhibitors combination therapy in patients with advanced CCA.MethodsAll patients with CCA who were consecutively admitted to the inpatient unit of our hospital and received PD-1 inhibitors combination therapy between September 2020 and April 2022 were screened. In total, 106 patients with CCA were screened out. We then followed up these patients until October 2022. Due to perioperative use (n=28), less than 2 cycles of PD-1 inhibitor therapy (n=9), incomplete data (n=8) and no pathological report (n=2), 59 patients were included in the final analysis. The patients were divided into the irAEs cohort and the non-irAEs cohort according to whether they experienced irAEs or not. The Log-Rank test was performed to compare the difference in survival time between these two cohorts. We then applied multivariate COX regression analysis to investigate whether irAEs were independent prognostic factors for survival in patients with advanced CCA.ResultsFinally, 32 patients were included in the irAEs cohort and 27 patients in the non-irAEs cohort. A total of 32 patients (54.2%) had any-grade irAEs, of which 4 patients (6.8%) had grade 3-4 irAEs. The most common irAEs were thyroid toxicity (30.5%) and dermatologic toxicity (30.5%). There were no notable differences in demographics and clinical characteristics between the irAEs and non-irAEs cohorts, except for total bilirubin level (P=0.026) and relapse (P=0.016). The disease control rate (DCR) in the irAEs cohort was higher than in the non-irAEs cohort (90.6% vs 70.4%, P=0.047). Median overall survival (OS) and median progression-free survival (PFS) were better in the irAEs cohort than in the non-irAEs cohort (OS: 21.2 vs 10.0 months, P<0.001; PFS: 9.0 vs 4.4 months, P=0.003). Multivariate COX regression analysis showed that irAEs were independent prognostic factors for OS and PFS (OS: HR=0.133, 95% CI: 0.039-0.452, P=0.001; PFS: HR=0.435, 95% CI: 0.202-0.934, P=0.033).ConclusionIrAEs correlated with improved DCR, OS, and PFS in advanced CCA patients receiving PD-1 inhibitors combination therapy.

show abstract

“… 4 Based on the TOPAZ-1 trial, the National Comprehensive Cancer Network listed GemCis plus durvalumab as a category 1 recommendation for first-line therapy of advanced BTC. 2 , 5 Although BTC can be immunogenic, the infiltration of immunosuppressive immune cells is implicated in tumour immune escape. Moreover, the tolerogenic liver environment further enhances immunosuppression, because cancers may utilise this mechanism to promote immune tolerance and potentially resist ICI treatment.…”

Section: Introductionmentioning

confidence: 99%

Immuno-genomic-radiomics to predict response of biliary tract cancer to camrelizumab plus GEMOX in a single-arm phase II trial

Liu

Tang²,

Chen

et al. 2023

JHEP Reports

View full text Add to dashboard Cite

Cholangiocarcinoma: what are the options in all comers and how has the advent of molecular profiling opened the way to personalised medicine ?

Cited by 18 publications

References 83 publications

Degradation of AZGP1 suppresses apoptosis and facilitates cholangiocarcinoma tumorigenesis via TRIM25

Degradation of AZGP1 suppresses apoptosis and facilitates cholangiocarcinoma tumorigenesis via TRIM25

Immune-related adverse events correlate with the efficacy of PD-1 inhibitors combination therapy in advanced cholangiocarcinoma patients: A retrospective cohort study

Immuno-genomic-radiomics to predict response of biliary tract cancer to camrelizumab plus GEMOX in a single-arm phase II trial

Contact Info

Product

Resources

About