Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (IDH1), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients.
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PMID:Molecular profiling of biliary tract cancer: a target rich disease. 2774 93

Worldwide hepatobiliary cancers are the second leading cause of cancer related death. Despite their relevance, hepatobiliary cancers have a paucity of approved systemic therapy options. However, there are a number of emerging therapeutic biomarkers and therapeutic concepts that show promise. In hepatocellular carcinoma, nivolumab appears particularly promising and recently received US FDA approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1 and immune checkpoint inhibitors are the furthest along and generating the most excitement. There are additional biomarkers that merit further exploration in hepatobiliary cancers including FGF19, ERRFI1, TERT, BAP1, BRAF, CDKN2A, tumor mutational burden and ERBB2 (HER2/neu). Development of new and innovative therapies would help address the unmet need for effective systemic therapies in advanced and metastatic hepatobiliary cancers.
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PMID:Novel targeted therapy strategies for biliary tract cancers and hepatocellular carcinoma. 2946 Jun 42

Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often identified at an advanced stage and have poor prognoses. Although effective chemotherapy regimens are needed, their development remains unsatisfactory. From the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus cisplatin is the standard first-line chemotherapeutic regimen for advanced biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs. gemcitabine plus S-1 therapy (FUGA-BT) demonstrated the non-inferiority of gemcitabine plus S-1 to gemcitabine plus cisplatin. A phase III trial of gemcitabine plus cisplatin vs. gemcitabine plus cisplatin plus S-1 (MITSUBA) was conducted, and the report on the results of the final analysis is being awaited. A standard second-line chemotherapeutic regimen has not yet been established. Fluoropyrimidines are frequently used in clinical practice. Despite many clinical trials being conducted with molecular targeted agents including erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib and vandetanib, no agent has shown to be effective for advanced biliary tract cancer. Next-generation sequencing shows great promise by allowing rapid mutational analysis of multiple genes in human cancers, and attractive driver genetic alterations have been reported in biliary tract cancer. FGFR2 fusion gene, mutations of IDH1/2, BRAF, BRCA1/2, ATM, PIK3CA and overexpression of c-MET and HER2/neu are reported relatively frequently and are interesting targets. Therefore, future development in precision medicine utilizing next-generation sequencing is expected. Although the efficacy of immune checkpoint inhibitors, such as anti-PD-1, anti-PD-L1 and anti-CTLA4 antibodies, remains unknown at present, basic data and results of ongoing clinical trials are anticipated.
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PMID:New developments in systemic therapy for advanced biliary tract cancer. 2989 94