1,721,005 research outputs found
Asbestos and Intrahepatic Cholangiocarcinoma
Full text linkThe link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development
Have We Found the “Holy Grail” That May Predict Response to Immunotherapy in Hepatocellular Carcinoma?
No full textN/
Mutational Landscape of Cholangiocarcinoma According to Different Etiologies: A Review
Full text linkRecent next-generation sequencing (NGS) studies on large cohorts of cholangiocarcinoma (CCA) patients have clearly revealed the extreme intra- and inter-tumoral molecular heterogeneity that characterizes this malignancy. The lack of a stereotyped molecular signature in CCA makes the identification of actionable therapeutic targets challenging, making it mandatory to have a better understanding of the origin of such heterogeneity in order to improve the clinical outcome of these patients. Compelling evidence has shown that the CCA genomic landscape significantly differs according to anatomical subtypes and the underlying etiology, highlighting the importance of conducting molecular studies in different populations of CCA patients. Currently, some risk factors have been recognized in CCA development, while others are emerging from recent epidemiological studies. Nevertheless, the role of each etiologic factor in driving CCA genetic heterogeneity still remains unclear, and available studies are limited. In an attempt to shed more light on this issue, here we review the current literature data on the mutational spectrum of this disease according to different etiologies
Improvements in Systemic Therapies for Advanced Malignant Mesothelioma
Full text linkMalignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies
Circulating tumor DNA in biliary tract cancer: Current evidence and future perspectives
No full textPeripheral blood of cancer patients “physiologically” presents cells and cellular components deriving from primary or metastatic sites, including circulating tumor cells (CTCs), circulating free DNA (cfDNA) and exosomes containing proteins, lipids and nucleic acids. The term circulating tumor DNA (ctDNA) indicates the part of cfDNA which derives from primary tumors and/or metastatic sites, carrying tumor-specific genetic or epigenetic alterations. Analysis of ctDNA has enormous potential applications in all stages of cancer management, including earlier diagnosis of cancer, identification of driver alterations, monitoring of treatment response and detection of resistance mechanisms. Thus, ctDNA has the potential to profoundly change current clinical practice, by moving from tissue to peripheral blood as a source of information. Herein, we review current literature regarding the potential role for ctDNA in biliary tract cancer (BTC) patients, with a particular focus on state-of-the-art techniques and future perspectives of this highly aggressive disease
Cholangiocarcinoma: Epidemiology and risk factors
Full text linkCholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. These differences are likely to reflect differences in geographical risk factors as well as genetic determinants. Of note, over the past few decades, the incidence rates of CCA appear to change and subtypes of CCA appear to show distinct epidemiological trends. These trends need to be interpreted with caution given the issues of diagnosis, recording and coding of subtypes of CCA. Epidemiological evidences suggest that in general population some risk factors are less frequent but associated with a higher CCA risk, while others are more common but associated with a lower risk. Moreover, while some risk factors are shared by intrahepatic and both extrahepatic forms, others seem more specific for one of the two forms. Currently some pathological conditions have been clearly associated with CCA development, and other conditions are emerging; however, while their impact in increasing CCA risk as single etiological factors has been provided in many studies, less is known when two or more risk factors co-occur in the same patient. Moreover, despite the advancements in the knowledge of CCA aetiology, in Western countries about 50% of cases are still diagnosed without any identifiable risk factor. It is therefore conceivable that other still undefined etiologic factors are responsible for the recent increase of CCA (especially iCCA) incidence worldwide
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.
No full textFibroblast growth factor (FGF) signalling via FGF receptors (FGFR1-4) orchestrates fetal development and contributes to tissue and whole-body homeostasis, but can also promote tumorigenesis. Various agents, including pan-FGFR inhibitors (erdafitinib and futibatinib), FGFR1/2/3 inhibitors (infigratinib and pemigatinib), as well as a range of more-specific agents, have been developed and several have entered clinical use. Erdafitinib is approved for patients with urothelial carcinoma harbouring FGFR2/3 alterations, and futibatinib and pemigatinib are approved for patients with cholangiocarcinoma harbouring FGFR2 fusions and/or rearrangements. Clinical benefit from these agents is in part limited by hyperphosphataemia owing to off-target inhibition of FGFR1 as well as the emergence of resistance mutations in FGFR genes, activation of bypass signalling pathways, concurrent TP53 alterations and possibly epithelial-mesenchymal transition-related isoform switching. The next generation of small-molecule inhibitors, such as lirafugratinib and LOXO-435, and the FGFR2-specific antibody bemarituzumab are expected to have a reduced risk of hyperphosphataemia and the ability to overcome certain resistance mutations. In this Review, we describe the development and current clinical role of FGFR inhibitors and provide perspective on future research directions including expansion of the therapeutic indications for use of FGFR inhibitors, combination of these agents with immune-checkpoint inhibitors and the application of novel technologies, such as artificial intelligence
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