Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to improve glucose and lipid homeostasis, promote weight loss, and reduce cardiovascular risk factors. They are a promising therapeutic option for non-alcoholic fatty liver disease (NAFLD), the most common liver disease, associated with T2DM, obesity, and metabolic syndrome. GLP-1RAs have been approved for the treatment of T2DM and obesity, but not for NAFLD. Most recent clinical trials have suggested the importance of early pharmacologic intervention with GLP-1RAs in alleviating and limiting NAFLD, as well as highlighting the relative scarcity of in vitro studies on semaglutide, indicating the need for further research. However, extra-hepatic factors contribute to the GLP-1RA results of in vivo studies. Cell culture models of NAFLD can be helpful in eliminating extrahepatic effects on the alleviation of hepatic steatosis, modulation of lipid metabolism pathways, reduction of inflammation, and prevention of the progression of NAFLD to severe hepatic conditions. In this review article, we discuss the role of GLP-1 and GLP-1RA in the treatment of NAFLD using human hepatocyte models.

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

The rapid evolution of sequencing technologies has profoundly advanced precision oncology. Whole-exome sequencing (WES), whole-genome sequencing (WGS), and whole-transcriptome sequencing (RNA-Seq) enable comprehensive characterization of tumor biology by detecting actionable mutations, gene fusions, splice variants, copy number alterations, and pathway dysregulation. These approaches also provide critical insights into biomarkers such as homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI), which are increasingly essential for guiding therapeutic decisions. Importantly, comprehensive genomic profiling not only refines patient stratification for targeted therapies but also sheds light on tumor–immune interactions and the tumor microenvironment, paving the way for more effective immunotherapeutic combinations. WGS is considered the gold standard for detecting germline mutations and complex structural variants, while WES remains central for detecting somatic driver mutations that guide targeted therapies. RNA-Seq complements these methods by capturing gene expression dynamics, identifying clinically relevant fusions, and revealing mechanisms of resistance. Together with advances in bioinformatics and artificial intelligence, these tools translate molecular data into actionable strategies for patient care. This review integrates insights from WGS, WES, and RNA-Seq with an overview of FDA- and EMA-approved targeted therapies, organized by tumor type, and highlights the molecular signaling pathways that drive cancer development and treatment. By bridging genomic profiling with regulatory-approved therapies, we outline current advances and future perspectives in delivering personalized cancer care.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing global health problem linked to obesity, insulin resistance, and dyslipidemia. MASLD often leads to fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, therapeutic options are limited, emphasizing the need for novel, targeted pharmacological interventions. Resmetirom, a selective thyroid hormone receptor beta (THR-β) agonist, offers a promising approach by specifically enhancing hepatic metabolism while minimizing systemic effects. Clinical trials have demonstrated its capacity to reduce hepatic triglyceride accumulation and improve lipid profiles. Early- and advanced-phase studies, including the MAESTRO program, highlight significant reductions in hepatic fat content and favorable impacts on noninvasive biomarkers of fibrosis with minimal side effects. This review highlights evidence from pivotal studies, explores resmetirom’s mechanism of action, and compares its efficacy and safety with other emerging therapeutic agents. While resmetirom marks a breakthrough in non-cirrhotic MASH management, further long-term studies are essential to fully evaluate its clinical benefits and potential regulatory approval for broader use in MASLD and MASH.