Systemic therapies for intrahepatic cholangiocarcinoma

Kelley, Robin Kate; Bridgewater, John; Gores, Gregory J.; Zhu, Andrew X.

doi:10.1016/j.jhep.2019.10.009

Cited by 294 publications

(223 citation statements)

References 92 publications

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“…At present, the clinical data on immunotherapy in CCA and other biliary tract cancers are limited and several trials are ongoing exploring, for instance, the role of monoclonal antibodies ipilimumab or tremelimumab (anti-CTL4) or antibodies targeting PD-L1, such as durvalumab, or its receptor programmed cell death protein 1 (PD-1), such as pembrolizumab or nivolumab [33,100].…”

Section: Checkpoints Inhibitors (Icis)mentioning

confidence: 99%

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Massironi

Pilla

Elvevi

et al. 2020

Cells

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Cholangiocarcinoma (CCA) represents a disease entity that comprises a heterogeneous group of biliary malignant neoplasms, with variable clinical presentation and severity. It may be classified according to its anatomical location and distinguished in intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), each subtype implying distinct epidemiology, biology, prognosis, and strategy for clinical management. Its incidence has increased globally over the past few decades, and its mortality rate remains high due to both its biological aggressiveness and resistance to medical therapy. Surgery is the only potentially curative treatment and is the standard approach for resectable CCA; however, more than half of the patients have locally advanced or metastatic disease at presentation. For patients with unresectable CCA, the available systemic therapies are of limited effectiveness. However, the advances of the comprehension of the complex molecular landscape of CCA and its tumor microenvironment could provide new keys to better understand the pathogenesis, the mechanisms of resistance and ultimately to identify promising new therapeutic targets. Recently, clinical trials targeting isocitrate dehydrogenase (IDH)-1 mutations and fibroblast growth factor receptor (FGFR)-2 fusions, as well as immunotherapy showed promising results. All these new and emerging therapeutic options are herein discussed.

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Section: Checkpoints Inhibitors (Icis)mentioning

confidence: 99%

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Massironi

Pilla

Elvevi

et al. 2020

Cells

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“…New systemic therapies, including immune-based therapies and biomarker-driven therapies, have been applied to treat iCCA [4]; however, the prognosis of this intractable disease remains dismal.…”

Section: Discussionmentioning

confidence: 99%

“…The introduction of new systemic therapies, including immune-based therapies and biomarker-driven therapies, has significantly improved the survival of patients with hepatobiliary cancers, particularly in the advanced stages of disease [2]. However, the prognosis of iCCA patients remains dismal, and surgical resection with negative resection margins and/or liver transplantation is the only curative treatment option [3,4].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Three-gene Signature Acting as a Novel Prognostic Biomarker in Intrahepatic Cholangiocarcinoma Patients

Tang¹,

Hunag²,

Li³

et al. 2020

Preprint

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Background: Intrahepatic cholangiocarcinoma (iCCA) patients have poor outcomes due to the lack of biomarkers for the selection of treatment options. The present study was conducted to find biomarkers with independent prognostic vaule in iCCA patients. Methods: Gene transcriptome profiles of E-MTAB-6389, TCGA-CHOL and GSE26566 were obtained from ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, respectively. Bioinformatic analyses were performed to screen novel biomarkers for predicting the prognosis of iCCA patients. Using multivariate Cox regression analyses, a 3-gene signature (BTD-FER-COL12A1) with potential prognostic value was identified and validated in both a training cohort and two validation cohorts. Results: A total of 177 iCCA patients were included in this study. From the key gene modules significantly associated with liver cirrhosis and overall survival (OS) of iCCA patients, we identified 89 hub genes for functional analyses. Cox-regression analyses in both the training and validation cohort indicate that FER, COL12A1 and BTD were independent risk factors for iCCA patients. A 3-gene signature (BTD-FER-COL12A1) with independent prognostic value in iCCA patients was validated in the training cohort, as well as in two validation cohorts. In terms of predicting the prognosis of iCCA patients, the receiver operating characteristics (ROC) curves showed that this 3-gene signature had superior prediction power to BTD, FER, and COL12A1 alone, as well as known biomarkers (MUC1, MUC13) of iCCA. Immunohistochemical staining of samples from The Human Protein Atlas showed that FER and COL12A1 were positively expressed in iCCA tissue, although BTD was not, while none of these genes was detected in normal tissue. These findings were consistent with the expression status of BTD, FER and COL12A1 at the transcriptional level. In addition, we found that FER and COL12A1 were significantly associated with the degree of infiltration by tumor-infiltrating immune cells. Conclusion: We discovered a three-gene signature with independent prognostic value as a novel biomarker for prediction prognosis of iCCA patients. Our findings may help to find novel therapeutic targets for precision treatment of iCCA.

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“…Landmark FDA approvals for various strategies, including immune checkpoint inhibitor (ICI), targeting CTLA4 or the PD1/PDL1 axis have dramatically impacted the lives of patients. Presently, the clinical data on immunotherapy in BTC are limited to small single-arm studies and sub-analyses of basket trials [3,105], though numerous clinical trials studying ICIs are underway (Tables 3, 4).…”

Section: Immunotherapymentioning

confidence: 99%

Systemic treatment options for advanced biliary tract carcinoma

et al. 2020

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Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC.

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Systemic therapies for intrahepatic cholangiocarcinoma

Cited by 294 publications

References 92 publications

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

Identification of a Three-gene Signature Acting as a Novel Prognostic Biomarker in Intrahepatic Cholangiocarcinoma Patients

Systemic treatment options for advanced biliary tract carcinoma

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