Novel approaches in search for biomarkers of cholangiocarcinoma

Cholangiocarcinoma(CCA)arises from the ductular epithelium of the biliary tree,either within the liver(intrahepatic CCA)or more commonly from the extrahepatic bile ducts(extrahepatic CCA).This disease has a poor prognosis and a growing worldwide prevalence.The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging,especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA,or distal CCA and pancreatic head adenocarcinoma.Most patients present with an advanced disease,unresectable disease,and there is a lack in non-surgical therapeutic modalities.Not least,there is an acute lack of prognostic biomarkers which further complicates disease management.Therefore,there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result,either singlehandedly or combined with other methods.In the"-omics"era,this goal can be attained by various means,as it has been successfully demonstrated in other primary tumors.Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins,metabolites,extracellular vesicles,and ultimately circulating tumor cells.However,given the relatively heterogeneous data,extracting clinical meaning from the inconsequential noise might become a tall task.The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.

Therapeutic advances of targeting receptor tyrosine kinases in cancer

Receptor tyrosine kinases(RTKs),a category of transmembrane receptors,have gained significant clinical attention in oncology due to their central role in cancer pathogenesis.Genetic alterations,including mutations,amplifications,and overexpression of certain RTKs,are critical in creating environments conducive to tumor development.Following their discovery,extensive research has revealed how RTK dysregulation contributes to oncogenesis,with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation,survival and progression.These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer.As a result,RTKs have emerged as primary targets in anticancer therapeutic development.Over the past two decades,this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors(TKIs),now effectively utilized in treating various cancer types.In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer.We explored the various alterations and overexpression of specific receptors across different malignancies,with special attention dedicated to the examination of current RTK inhibitors,highlighting their role as potential targeted therapies.By integrating the latest research findings and clinical evidence,we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.