The Lynx Group
Cholangiocarcinoma News

A Meta-Analysis of Novel Therapeutics for CCA

2020 Year in Review: Cholangiocarcinoma — December 19, 2020

Meta-analysis identifies upregulation of several novel genes that have not been previously described, and suggests the potential role of ERBB2 and extracellular genes in the pathogenesis of CCA.

There is great need for development of novel therapeutic strategies in CCA. A meta-analysis was conducted to better understand the pathobiology of CCA and identify novel candidate genes that might be potential targets for therapeutic intervention; results of this analysis were presented at the ASCO 2020 Gastrointestinal Cancers Symposium and summarized here.

In this analysis, the STARGEO platform was utilized to conduct a meta-analysis of public data from the National Center for Biotechnology Information’s Gene Expression Omnibus. The meta-analysis was performed with 259 CCA tumor samples and 16 normal intrahepatic duct samples (control). The gene signature of the samples was analyzed using Ingenuity Pathway Analysis.

The meta-analysis found that farnesoid X receptor/retinoid X receptor, liver X receptor/retinoid X receptor activation, coagulation system, and acute-phase response signaling, intrinsic prothrombin activation pathway were key canonical pathways implicated in pathogenesis of CCA. Several genes were found to be unregulated in CCA, many that have not been described in CCA, including extracellular matrix proteins (COL1A1, LAMC2), KRT17 (a keratin), and LAMB3 (PI3K/AKT signaling), as well as the immunophilin FKBP1A that is involved in mTOR activation, the ubiquitin-associated gene UBASH3B that inhibits endocytosis in EGFR. Significant upregulation of immune checkpoint proteins such as CTLA4 (P = .0289), TIGIT (P = .000310), and BTLA (P = .00949) were also observed. In addition, upregulation of SIGLEC7 (P = .0155) was documented, which is implicated in suppression of immune function. Several genes were also found to be downregulated, such as CELA3B, CPA1, CTRC, PLA2G1B, PRSS2, APOC2/4, CAP2, TTR, TAT, and F9. The potential role of ERBB2 in the regulation of oncogenes in CCA, including TP53, MYC, CDKN2A, and STAT3, was demonstrated. 

These results suggest the potential role of ERBB2 and extracellular genes in the pathogenesis of CCA and identified novel genes that were not previously described in CCA.

Source: Aljabban N, et al. J Clin Oncol. 2020;38(4_suppl). Abstract 584.

Related Items

Hot Topics in Cholangiocarcinoma and Biliary Tract Cancers: ASCO Highlights
September/October 2021, Vol 2, No 3
At the CCA Summit during the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), Mitesh J. Borad, MD, Associate Professor of Medicine, Mayo Clinic, Phoenix, AZ, reviewed some of the key topics presented at ASCO 2021 related to cholangiocarcinoma (CCA) and other biliary tract cancers. Before turning to the specific presentations, Dr Borad welcomed the May 28, 2021, FDA approval of infigratinib (Truseltiq) for patients with advanced or metastatic CCA and FGFR2 fusions or rearrangements. Infigratinib follows pemigatinib (Pemazyre) as the second targeted therapy now available for this patient population.
Important Role of Screening for Genomic Alterations in Cholangiocarcinoma
September/October 2021, Vol 2, No 3
Comprehensive molecular profiling has demonstrated a diverse landscape of oncogenic genomic alterations in cholangiocarcinoma (CCA), which are often the drivers of CCA. In a recent review article, Tanios S. Bekaii-Saab, MD, FACP, Vice Chair and Section Chief for Medical Oncology, Department of Internal Medicine, Mayo Clinic Cancer Center, Phoenix, AZ, and colleagues provided an overview of the molecular heterogeneity of CCA, discussing the role of molecular tests for the diagnosis of patients with intrahepatic CCA, and the implications of the genomic alterations in the treatment of patients with this aggressive disease.
Tibsovo First Targeted Therapy FDA Approved for Advanced or Metastatic CCA with IDH1 Mutation
September/October 2021, Vol 2, No 3
On August 25, 2021, the FDA approved ivosidenib (Tibsovo; Servier Pharmaceuticals), an oral IDH1 inhibitor, for the treatment of adults with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) and an IDH1 mutation, as detected by an FDA-approved test. The FDA granted ivosidenib a priority review for this indication and an orphan drug designation.
Role of Intraductal Treatment and Endoscopic Oncologists in the Management of Unresectable Extrahepatic Cholangiocarcinoma
September/October 2021, Vol 2, No 3
Although cholangiocarcinoma (CCA) is a rare cancer that originates in the bile ducts, its incidence rate continues to rise in the United States, and many patients are diagnosed late, with unresectable tumor and poor prognosis. The majority of patients with extrahepatic CCA, including the perihilar subtype, require referral to a center with expertise in endoscopic retrograde cholangiopancreatography (ERCP) and interventional radiology, because of the complexities in obtaining a definitive diagnosis and durable biliary drainage.
Role of Radiology in Intrahepatic Cholangiocarcinoma Addressed at 2 Interventional Oncology and Radiology Meetings
September/October 2021, Vol 2, No 3
Key topics related to intrahepatic cholangiocarcinoma (CCA) were presented at the 2021 Society of Interventional Oncology (SIO) and the Society of Interventional Radiology (SIR) meetings and were discussed at the CCA Summit. Bruno C. Odisio, MD, FSIR, Interventional Radiologist and Co-Director of Research, Interventional Radiology, M.D. Anderson Cancer Center, Houston, TX, reviewed the findings.
Ivosidenib Approved for Advanced or Metastatic Cholangiocarcinoma
Web Exclusives
Ivosidenib has been approved by the FDA for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 mutation as detected by an FDA-approved test.
Recent Developments in Genomic-Driven Therapies for Cholangiocarcinoma
June/July 2021, Vol 2, No 2
Personalized medicine has expanded the treatment options for patients with cholangiocarcinoma (CCA). At the 2021 Annual Meeting of the Cholangiocarcinoma Foundation (CCF), Ghassan K. Abou-Alfa, MD, MBA, Professor of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, discussed recent developments in personalized therapies, highlighting genomic alterations that are informing the new therapies for patients with CCA.
FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma
June/July 2021, Vol 2, No 2
The FDA granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) that harbors an FGFR2 fusion or other rearrangement.
Futibatinib in Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Rearrangements: Primary Results of FOENIX-CCA2 Presented at AACR 2021
June/July 2021, Vol 2, No 2
The primary results of the phase 2 FOENIX-CCA2 clinical trial of futibatinib in patients with previously treated intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements were presented by Lipika Goyal, MD, MPhil, Assistant Professor of Medicine, Massachusetts General Hospital, Boston, at the 2021 Annual Meeting of the American Association for Cancer Research (AACR).
Truseltiq (Infigratinib) New Targeted Therapy FDA Approved for Advanced or Metastatic Cholangiocarcinoma Harboring FGFR2 Alterations
By Loretta Fala
June/July 2021, Vol 2, No 2
Cholangiocarcinoma (CCA) represents a group of heterogeneous cancers that originate in the bile ducts that connect the liver and gallbladder to the small intestine. Although the exact prevalence of CCA is unknown, CCA is a rare cancer; approximately 8000 new cases of CCA are diagnosed annually in the United States.

Subscribe to CCA News

Stay up to date with personalized medicine by subscribing to receive the free CCA News print publication or weekly e‑Newsletter.

I'd like to receive: