Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is characterized by a high degree of clinical heterogeneity that is influenced by the disease’s molecular complexity. The genes most frequently affected in CLL cluster into specific biological pathways, including B-cell receptor (BCR) signaling, apoptosis, NF-κB, and NOTCH1 signaling. BCR signaling and the apoptosis pathway have been exploited to design targeted medicines for CLL therapy. Consistently, molecules that selectively inhibit specific BCR components, namely Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) as well as inhibitors of BCL2, have revolutionized the therapeutic management of CLL patients. Several BTK inhibitors and PI3K inhibitors with different modes of action are currently used or are in development in advanced stage clinical trials. Moreover, the restoration of apoptosis by the BCL2 inhibitor venetoclax offers meaningful clinical activity with a fixed-duration scheme. Inhibitors of the BCR and of BCL2 are able to overcome the chemorefractoriness associated with high-risk genetic features, including TP53 disruption. Other signaling cascades involved in CLL pathogenesis, in particular NOTCH signaling and NF-kB signaling, already provide biomarkers for a precision medicine approach to CLL and may represent potential druggable targets for the future. The aim of the present review is to discuss the druggable pathways of CLL and to provide the biological background of the high efficacy of targeted biological drugs in CLL.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide, owing to late-stage diagnosis and underlying liver disease that limits curative treatment options. Conventional surveillance and diagnostic strategies relying on imaging and alpha-fetoprotein (AFP) lack sufficient sensitivity, particularly for early-stage disease, underscoring the need for more accurate and minimally invasive approaches. Liquid biopsy has emerged as a promising investigational approach for early HCC detection and disease monitoring by enabling analysis of tumor-derived components in circulation. This review summarizes recent advances in liquid biopsy biomarkers for early-stage HCC, including genomic alterations in circulating tumor DNA (ctDNA), DNA methylation markers, circulating microRNAs, exosome-derived non-coding RNAs, and inflammatory markers. Established biomarkers such as AFP, together with complementary biomarkers including PIVKA-II, contribute to HCC risk assessment, while ctDNA alterations, particularly TERT promoter and TP53 mutations, provide insight into early tumorigenesis and molecular heterogeneity. Aberrant methylation of tumor suppressor genes, including RASSF1A , SEPT9 , and CDKN2A , represents early molecular events detectable in plasma. Circulating and exosomal microRNAs and long non-coding RNAs (lncRNAs) have demonstrated potential to improve diagnostic accuracy, particularly when incorporated into multi-marker panels. Importantly, these biomarkers vary in their level of clinical validation, ranging from guideline-integrated markers to emerging candidates that still require further standardization and prospective validation. Integrating validated biomarkers with novel epigenetic and RNA-based signatures holds substantial promise for improving early detection, patient stratification, and therapeutic decision-making in HCC.