sorafenib

We concluded for the first time that the combination of SOR and ASH-AE generates antagonistic antitumor effect in HepG2 cells. Moreover, ASH-AE can inhibit proliferation of HepG2 cells and mitigate sorafenib-induced resistance-associated markers in HepG2 cells by targeting CD90+ cells via Hedgehog pathway modulation.

With respect to drug response, PRKD1-high HCC cases exhibited increased predicted sensitivity to multiple tyrosine kinase inhibitors (TKIs), while in vitro PRKD1 knockdown reduced sorafenib sensitivity, and sorafenib treatment suppressed both PRKD1 and p-ERK1/2 levels. Collectively, our findings identify PRKD1 as a multifaceted contributor to HCC progression, immune microenvironment modulation, and TKI responsiveness. These results highlight PRKD1 as a promising therapeutic target warranting further mechanistic and translational investigation.

Herein, guided by the structural features of Sorafenib, the selective Bcl-2 inhibitor Venetoclax, and the selective Mcl-1 inhibitor AZD5991, we designed and synthesized a series of novel Sophocarpine-derived analogues bearing a pyridylethyl moiety via a molecular-hybridization strategy. In parallel, a 3D-QSAR (CoMFA) model was constructed to rationalize the structure-activity relationship and to inform further lead optimization. Collectively, these findings identify S6 as a promising Sophocarpine derivative with a putative dual Bcl-2/Mcl-1 targeting profile, with significant anti-HCC activity and potential for preclinical development.

Several compounds, particularly 6f and 6h-j, demonstrated potent cytotoxicity, with IC50 values as low as 4.82-10.23 µM against MCF-7 cells, surpassing reference drugs like sorafenib and doxorubicin. In silico studies indicated strong binding interactions of the compounds with kinases, and pharmacokinetic assessments revealed favorable properties. These findings underscore the potential of benzimidazole-hydrazone derivatives as effective cancer therapeutics, meriting further investigation into their mechanisms and clinical implications.

While first-line BEP (bleomycin, etoposide, cisplatin) chemotherapy achieves high cure rates in most patients, those who progress after multiple lines of therapy have a poor prognosis and limited treatment options, highlighting a critical gap in effective treatment decision-making for advanced disease...He then experienced rapid progression with new lung and brain metastases that were unresponsive to second-line GEMOX (gemcitabine + oxaliplatin) chemotherapy and a programmed death-ligand 1 (PD-L1) blockade clinical trial...Guided by a molecular tumor board (MTB) recommendation, an off-label regimen of carboplatin, paclitaxel, and sorafenib (CPS) was initiated, targeting the MAPK pathway...Tumors are highly complex, and gene-cancer interaction is still being elucidated. In this context, key learning points from this case include: 1) the critical role of iterative molecular profiling and MTB guidance in identifying actionable targets when standard options are exhausted; 2) the potential value of rational drug rechallenge informed by the evolving "tumor ecology;" and 3) the necessity of long-term follow-up to link treatment responses with biomarkers, allowing N-of-1 learning that may offer a template for personalized management in similarly challenging cases.

Conventional systemic therapies such as sorafenib and its successors provide only modest survival benefits and are frequently complicated by toxicity and drug resistance...Furthermore, interactions between exosomes and gut microbiota in modulating hepatic immunity represent an emerging frontier with unexplored therapeutic implications. Continued advances in bioengineering, nanotechnology, and systems biology are expected to refine exosome-based therapies, offering novel, personalized strategies to improve outcomes for HCC patients.

P=N/A, N=87, Not yet recruiting, Nanfang Hospital, Southern Medical University; Nanfang Hospital, Southern Medical University

Diff-Metabolic cells retained liver-specific functions with favorable prognosis, whereas the other three programs correlated with disease advancement; notably, all four states exhibited differential therapeutic vulnerabilities, including sorafenib resistance...Geneformer-based virtual knockout screening identified HSP90B1 as a convergent dependency, validated by its cancer cell essentiality, HCC overexpression, abundance in treatment-resistant tumors, and association with adverse survival. This integrated atlas establishes a framework for targeting tumor-intrinsic states and microenvironmental dependencies in HCC.

Strikingly, subtherapeutic doses of rottlerin enhanced the efficacy of clinical ferroptosis inducers (RSL3 and sorafenib), and this chemosensitization effect persisted in PKCδ-depleted models, indicating a target-agnostic mechanism. Our work provides the first demonstration of rottlerin's ferroptotic activity in HCC, positioning it as a dual degrader capable of overcoming compensatory antioxidant adaptations. These findings advocate for rottlerin's clinical development either as monotherapy or in rational combinations to augment ferroptosis-targeted HCC treatment.

YsF-LSG peptide mixtures reverse SFR of HCC through G3BP2-recruited, SGs-targeting and apoptosis-restored mechanisms. This provides a new strategy for developing enzyme-induced LLPS peptide coacervates with drug resistance-reversal capacity.

The nine-lncRNA signature exhibits robust predictive power for HCC prognosis and provides novel insights into the mechanisms of lncRNA-regulated palmitoylation in HCC development.