Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy

  title={Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy},
  author={Alphonse E. Sirica},
  • A. Sirica
  • Published 1 January 2005
  • Biology, Medicine
  • Hepatology
Cholangiocarcinomas are devastating cancers that are increasing in both their worldwide incidence and mortality rates. The challenges posed by these often lethal biliary tract cancers are daunting, with conventional treatment options being limited and the only hope for long‐term survival being that of complete surgical resection of the tumor. Unfortunately, the vast majority of patients with cholangiocarcinoma typically seek treatment with advanced disease, and often these patients are deemed… 

Molecular Targets in Biliary Carcinogenesis and Implications for Therapy.

A comprehensive review of targeted therapies in biliary tract cancers was undertaken to present emerging evidence from laboratory and/or molecular studies as they translate to clinical trials and outcomes.

Biliary tract carcinoma: clinical perspectives on molecular targeting strategies for therapeutic options

The outcomes of recent studies have revealed, in detail, the molecular mechanism of carcinogenesis and tumor progression of BTC, and these studies have exploited select molecular targets that could significantly impact the clinical outcome.

Pathogenesis and Therapeutic Targets of Cholangiocarcinoma

A detailed review of the pathogenesis of cholangiocarcinoma and its relevance in molecular targets for potential therapies in cholanigans, and the understanding of the prognostic difference within this disease is begun.

The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer

There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease and a bedside-to-bench approach to discussing cholangiocarcinoma is taken and research opportunities for the future are outlined.

Intrahepatic Cholangiocarcinoma: A Summative Review of Biomarkers and Targeted Therapies

Although rare, intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy and the incidence of ICC has increased 14% per year in recent decades.

Diagnosis and management of cholangiocarcinoma

Advances in understanding the pathogenesis of CC, including the role of oncogenes, inflammation-mediated genomic instability, and interleukin-6/STAT-3 signaling pathways, may allow development of new diagnostic and prognostic markers and targets for CC therapy.

Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009.

Magnetic resonance imaging/magnetic resonance cholangiopancreatography, positron emission tomography scan, endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.

Cholangiocarcinoma development: The resurgence of bile acids

It is proved that taurocholic acid (TCA) exerts proproliferative effects on rat and human cell lines that are blocked by treatment with JTE-013 or by shRNA knockdown of S1PR2, a new bile acid receptor identified recently.

Reappraisal of the Therapeutic Role of Celecoxib in Cholangiocarcinoma

It is concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA, but its clinical application still needs more studies to prove its safety.

The role of microRNAs in liver cancer

An obvious need emerges for the discovery of new biomarkers to understand the events leading to hepatocarcinogenesis, to relate different phenotypes with differences in clinical behavior and prognosis, and, if possible, to predict response rates to adjuvant therapeutic modalities or to establish novel mechanism-based treatments for hepatic tumors.



A Review and Update on Cholangiocarcinoma

This review discusses epidemiology, etiologic factors, molecular pathogenesis, diagnosis, staging, and treatment of cholangiocarcinoma, with particular focus on recent studies into the cellular and molecular pathogenic of the disease, recent chemotherapy trials, and newer methods of staging and screening.

Diagnosis and treatment of cholangiocarcinoma

Liver transplantation for unresectable cholangiocarcinoma was shown to be feasible in pilot studies of highly selected patients and genetic aberrations in brush cytology specimens should be explored further in prospective studies.

A study of carboplatin‐coated tube for the unresectable cholangiocarcinoma

A new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin‐coated tube; CCT) showed an antitumor effect on human cholangiocarcinoma cell line HuCC‐T1 in vitro and may provide a new treatment modality for this disease.

MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma‐mass forming type

Results suggest that expression of MUC4 in ICC‐MF is a new independent factor for poor prognosis and is a useful marker to predict the outcome of the patients with ICC‐ MF.

Biliary cancer growth factor pathways, cyclo‐oxygenase‐2 and potential therapeutic strategies

It is proposed that the selective therapeutic targeting of aberrant growth factor receptor tyrosine kinase signaling and of cyclo‐oxygenase‐2, alone or in combination, has potential to become a useful new approach for the treatment and/or chemoprevention of cholangiocarcinoma.

Intrahepatic cholangiocarcinoma: indication for transplantation.

Generally speaking, IH-CCC is not a favorable indication for liver transplantation, however, there is a highly selected group of patients with early tumor stages potentially benefitting from LTx, and combination with neoadjuvant chemoirradiation may further improve results after LTx.

Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma.

The known mechanisms involved in the carcinogenesis of biliary epithelium are addressed and established and hypothetical future therapeutic strategies directed towards specific pathogenetic events during biliary carcinogenesis will be addressed.

COX-2 inhibition and colorectal cancer.

Recent studies have identified a potential benefit for adding celecoxib to standard CRC chemotherapy regimens to increase their efficacy and reduce their associated toxicity.