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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Due to the many limitations of the EGFR/HER1 tyrosine kinases, the role of pan-HER inhibitors has become more significant as they can potentially block other signaling pathways associated with EGFR/HER1. Studies suggest that pan-HER inhibitors are most effective in patients harboring activating EGFR mutations, although some clinical benefit has also been observed in patients without activating mutations. The best-known Pan-Her2 inhibitors are afatinib (Gilotrif™ and Giotrif™), neratinib (NerlynxTM), and dacomitinib (VizimproTM), which were first approved by the FDA in 2013, 2017, and 2018, respectively, for the treatment of HER-2 positive breast cancer. They are also recommended by NICE for use in the UK. It was announced in late 2019 that another pan-HER inhibitor, varlitinib, developed by Aslan Pharmaceuticals, did not meet its primary endpoints of progression-free survival (PFS) and overall response rate (ORR) in second-line biliary tract cancer (BTC) patients in a pivotal clinical trial, and is not being progressed.
Cytokine Regulation of Cholangiocyte Growth
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
The effects of TGFβ on cholangiocyte proliferation may be mediated indirecdy through matrix-cell interactions since this cytokine is a potent mediator of the stromal reaction. Bile duct cancer is often accompanied by abundant fibrous stroma. Expression of TGFβ1 in biliary tract cancer cells correlates with collagen type I expression.29 Yazumi et al. reported that three of five bile duct carcinoma cell lines had disruption of TGFβ signaling including the loss of Smad 4 expression and the heterozygous deletion of TβRII.26 In these cases, abundant interstitial fibrosis was found in xenograft of TGFβ resistant cells, but not of TGFβ sensitive tumor suggesting that deregulated TGFβ signaling may also correlate with stromal cell reaction during tumor cell invasion.
The Gallbladder and Bile Ducts
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
A minority of patients presenting with cholangiocarcinoma have a known risk factor. The major risk factor in Western practice is primary sclerosing cholangitis (PSC). It is estimated that a long-standing history of PSC increases the risk of developing biliary tract cancer by 20-fold compared to the normal population. It appears that patients with PSC and concomitant inflammatory bowel disease are at significantly higher risk of developing cancer compared to those without the disease. Cholangiocarcinoma appears to occur at an earlier age in patients with PSC (30-50 years of age) compared to the general population. In addition, disease is usually multifocal and detected at advanced stage with resultant poor prognosis.
Prognostic Nutritional Index Associates with Immunotherapy Response in Patients with Metastatic Biliary Tract Cancer
Published in Nutrition and Cancer, 2023
Lei Yang, Juan Zhong, Wenbo Wang, Fuxiang Zhou
The outcomes of 107 patients with metastatic biliary tract cancer were evaluated retrospectively. In chemotherapy cohort, 48 patients with metastatic biliary tract cancers received first-line chemotherapy treatment at our center during the study period from March 2017 to April 2022. Of these, seven patients had no post-baseline assessment, and 9 had no follow-up data, leaving 32 eligible patients. Meanwhile, in ICIs cohort, 59 patients with metastatic biliary tract cancers received ICIs treatment at our center during the same study period. Of these, two patients had no post-baseline assessment, and 6 had no follow-up data, leaving 51 eligible patients. 31 patients received first-line immunotherapy. Detailed patient characteristics are presented in Table 1. The median follow-up time was 12 mo, (range 2–60 mo).
Circulating miRNA and cell-free DNA as a potential diagnostic tool in early detection of biliary tract cancer: a meta-analysis
Published in Biomarkers, 2022
Aakansha Singh, Anjana Dwivedi
An accurate and effective diagnosis remains a limitation in the early detection of biliary tract cancer (BTC). Steadily increasing BTC cases require the development of a sensitive and reliable diagnostic tool. The result of our meta-analysis aids in the following significance for the clinical field:This study includes liquid biopsy-based biomarkers [microRNA (miRNA), cell-free DNA (cfDNA), and circulating tumour cells (CTC)] that can be potentially more significant than the existing tissue biopsy technique.The high sensitivity %age of these biomarkers derived from this meta-analysis (miRNA: 0.84, cfDNA: 0.89, CTC: 0.75) suggests that they are a promising candidate for the diagnosis of BTC.The area under curve plotted for the biomarkers (miRNA: 0.956, cfDNA: 0.983, CTC: 0.9556) reports their robustness and hence can be further considered for BTC diagnosis.Results of the present meta-analysis report the potential of miRNA, cfDNA, and CTC as a diagnostic tool in BTC.
Clinical insights and prognostic factors from an advanced biliary tract cancer case series: a real-world analysis
Published in Journal of Chemotherapy, 2022
Roberto Filippi, Francesco Leone, Lorenzo Fornaro, Giuseppe Aprile, Andrea Casadei-Gardini, Nicola Silvestris, Andrea Palloni, Maria Antonietta Satolli, Mario Scartozzi, Marco Russano, Stefania Eufemia Lutrino, Pasquale Lombardi, Giorgio Frega, Silvio Ken Garattini, Caterina Vivaldi, Rosella Spadi, Orsi Giulia, Elisabetta Fenocchio, Oronzo Brunetti, Massimo Aglietta, Giovanni Brandi
Biliary tract cancer (BTC) comprises a spectrum of epithelial malignancies arising from the biliary tree, with varying composition (intrahepatic cholangiocarcinoma [ICC]; distal and proximal extrahepatic cholangiocarcinoma [dECC, pECC]; gallbladder cancer [GC]) according to the geographic region [1]. Ampullary cancer (AC) is often regarded as an additional primary site of BTC [2–4]. Southern Europe has a higher incidence of BTC than Northern European countries [5]. Italy, where BTC accounts for 1% of new cancer diagnoses, lies among the intermediate-incidence countries [1, 6]. Due to the tendency to relapse after resection, and the aggressiveness and resistance to chemotherapy (CT) in the advanced setting (aBTC), prognosis of these patients (pts) is dismal [1, 7–10]. In 2010, the cisplatin-gemcitabine (gem) doublet (GemCis) emerged as the standard first-line CT (CT1) in the BT-22 and ABC-02 trials [11, 12]. In contrast, only recently data from the ABC-06 trial supported mFOLFOX as a candidate for standard second-line CT (CT2) [13]. Targeted and immunologic therapies do not yet represent a standard treatment option in BTC pts [14–16].