Using genome editing, a group led by scientists from Zhejiang University has created a collection of mouse models of primary liver cancer (PLC) that could serve as a resource for research and drug development. While PLC is the third leading cause of cancer-related mortality globally, its heterogeneity limits efforts to develop precision treatments. In a study appearing in Science Advances this week, the researchers used in situ genome editing of hepatocytes to generate 25 mouse models of PLC that recapitulate 25 single or combinations of human cancer driver genes. The mouse tumors cover the major histopathological types of human PLCs and can be divided into three human-matched molecular subtypes based on transcriptomic and proteomic profiles. The study authors use the models to find subtype- or genotype-specific alterations in immune microenvironment, metabolic reprogramming, cell proliferation, and expression of drug targets, as well as to identify a protein involved in metabolic reprogramming and liver tumorigenesis. "Our data can be a valuable resource for mechanistic study of heterogeneous abnormalities in liver cancer and for the evaluation of novel therapies in a preclinical setting, which may thus fill the gap in translating molecular subtyping to clinics," they write.
By analyzing genomic and other data of Hürthle cell carcinoma (HCC), a Memorial Sloan Kettering Cancer Center-led team has uncovered new insights into the metabolic and microenvironmental aspects of this rare but deadly malignant subtype of thyroid cancer. In the study, which appears in Science Advances this week, the investigators performed metabolomic, transcriptomic, and immunophenotypic profiling of HCC and other thyroid tumors. The work reveals the characteristic, metabolomic, and microenvironmental features of HCC, as well as their relation to the disease's two exceptional genotypes: mitochondrial DNA mutations and near genome-wide chromosomal loss of heterozygosity. The work, they write, highlights the profound metabolic reorganization of mitochondrial metabolism in many thyroid cancers and the characteristic changes to specific metabolic pathways unique to HCC.