Novel Treatments for Advanced Cholangiocarcinoma

Cotton, Jenny; Lamarca, Ángela; McNamara, Mairéad G.; Valle, Juan W.

doi:10.1007/978-3-319-92216-4_18

Cited by 1 publication

(1 citation statement)

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“…Other valid options for patients with localized unresectable CCAs are locoregional therapies, based on the focalized delivery of chemotherapy and radiotherapy. Techniques such as transarterial chemoembolization (TACE) and transarterial radioembolization (TARE), hepatic arterial-based therapies (HAT), radiofrequency ablation and photodynamic therapy (PDT) can increase survival and improve local control in locally advanced-metastatic iCCAs [9], although recurrence rates remain high [3]. In the field of innovative potential cancer treatment strategies, the use of non-toxic functionalized nanostructures, such as gold nanoparticles (AuNPs) [10] or graphene oxide nanosheets (GOxNs) [11], represent promising alternative systems to deliver chemotherapeutic agents selectively to tumor cells, reducing the drug exposure of normal cells.…”

Section: Cholangiocarcinoma: From Classification To Treatment Strategiesmentioning

confidence: 99%

IDH1 Targeting as a New Potential Option for Intrahepatic Cholangiocarcinoma Treatment—Current State and Future Perspectives

et al. 2020

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Cholangiocarcinoma is a primary malignancy of the biliary tract characterized by late and unspecific symptoms, unfavorable prognosis, and few treatment options. The advent of next-generation sequencing has revealed potential targetable or actionable molecular alterations in biliary tumors. Among several identified genetic alterations, the IDH1 mutation is arousing interest due to its role in epigenetic and metabolic remodeling. Indeed, some IDH1 point mutations induce widespread epigenetic alterations by means of a gain-of-function of the enzyme, which becomes able to produce the oncometabolite 2-hydroxyglutarate, with inhibitory activity on α-ketoglutarate-dependent enzymes, such as DNA and histone demethylases. Thus, its accumulation produces changes in the expression of several key genes involved in cell differentiation and survival. At present, small-molecule inhibitors of IDH1 mutated enzyme are under investigation in preclinical and clinical phases as promising innovative treatments for IDH1-mutated intrahepatic cholangiocarcinomas. This review examines the molecular rationale and the results of preclinical and early-phase studies on novel pharmacological agents targeting mutant IDH1 in cholangiocarcinoma patients. Contextually, it will offer a starting point for discussion on combined therapies with metabolic and epigenetic drugs, to provide molecular support to target the interplay between metabolism and epigenetics, two hallmarks of cancer onset and progression.

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