title: Deciphering the role of mutant-IDH1 in liver cancer development and the tumor immune microenvironment creator: Fernández Vaquero, Mirian Concepción subject: ddc-500 subject: 500 Natural sciences and mathematics subject: ddc-570 subject: 570 Life sciences description: Primary liver cancer (PLC) is among the five deadliest cancers worldwide, which represents a clinical challenge to the global health system. Anatomically arising from a regenerative organ with high capacity for plasticity as the liver, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the most frequent types of PLC. Although iCCA represents just 10-20% of liver tumors, the rise in its incidence in the past decades urges to develop new strategies that facilitate patient stratification and offer the best particular therapies and outcomes. Due to the limited treatment options and the considerable heterogeneity that this malignancy displays on distinct levels, integrative analyses have been key to identify targetable alterations that may improve the clinical management of this disease. Notably, gain-of-function mutations in the IDH1 gene, which lead to the accumulation of the oncometabolite 2-HG, have been commonly reported in 15-20% of iCCA cases. Mutant-IDH1 plays a pivotal role in the deregulation of homeostatic processes, strongly affecting the tumor immune microenvironment (TIME) and promoting cancer development. Nevertheless, further research is needed to decipher the intra- tumor heterogeneity and the molecular underpinnings by which mutant-IDH1 enhances cholangiocarcinogenesis. date: 2024 type: Dissertation type: info:eu-repo/semantics/doctoralThesis type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/33608/1/PhD%20thesis_MirianFernandezVaquero.pdf identifier: DOI:10.11588/heidok.00033608 identifier: urn:nbn:de:bsz:16-heidok-336082 identifier: Fernández Vaquero, Mirian Concepción (2024) Deciphering the role of mutant-IDH1 in liver cancer development and the tumor immune microenvironment. [Dissertation] relation: https://archiv.ub.uni-heidelberg.de/volltextserver/33608/ rights: info:eu-repo/semantics/openAccess rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html language: eng