Patchouli alcohol (PA) is a tricyclic sesquiterpene derived from Pogostemon cablin, and the present study evaluated the antihepatoma capacity of PA and described a potential strategy for its combination with sorafenib (SOR) in vitro and in vivo...On the whole, PA alone or in combination with SOR exhibited markedly improved therapeutic efficacy in HCC by blocking AR-mediated and multiple other signaling pathways. Therefore, this study provides an experimental basis for the evaluation of PA as an alternative drug (alone or in combination) for the treatment of HCC.

Compound 9a displayed strong inhibitory activity against VEGFR-2, with an IC50 value of 0.23 ± 0.03 μM, comparable to that of sorafenib...Docking within the VEGFR-2 active site supported the biological findings by revealing promising binding interactions. Besides, ADME analysis supports the design strategy and suggests that these derivatives possess promising pharmacokinetic properties.

Knockdown of PRPF4B triggers ROS-dependent DNA damage, cell cycle arrest, and suppression of HCC proliferation, while enhancing sorafenib sensitivity via inhibition of the NF-κB pathway. Therefore, PPRF4B may be a potential therapeutic target for HCC treatment and sorafenib sensitization.

This study investigated the immunomodulatory effects of DAMPs released from HepG2 cells treated with standard chemotherapeutic agents, sorafenib and oxaliplatin. Although the cytokine profile was predominantly pro-inflammatory (TNF-α, IL-1β), the concurrent secretion of IL-10 suggests a complex, mixed activation state. By overriding M2 immunosuppression via an ERK-NLRP3-dependent pathway, sorafenib-derived DAMPs act as an immunological primer to convert cold to hot tumors, providing a molecular rationale for chemo-immunotherapy combinations.

PRS was used to optimize GACC-metformin-regorafenib combinations...In zebrafish xenografts, GACC (50 µM) reduced Hep3B tumor fluorescence by ~90% without detectable hepatotoxicity, whereas sorafenib decreased liver size/fluorescence...PRS identified an off-grid triple combination that reduced PLC/PRF/5 viability to 19% while maintaining THLE-2 viability at 52% and preserving zebrafish development. GACC is a G4-active cobalt-glutamate scaffold with anti-HCC activity and favorable zebrafish safety, and a zebrafish-plus-PRS workflow enables rational, less toxic combination design.

We treated the embedded cells or spheroids with different concentrations of either sorafenib or vemurafenib to investigate drug response. We showed that our 3D model was able to reproduce the findings of the in vivo studies, as we observed resistance to the drug in response to sorafenib treatment after 4 weeks. Taken together, the results of this study highlight the potential of user-friendly alginate 3D cell culture models for several aspects of melanoma drug development.

The new candidates showed considerable in vitro activity against MDA-MB-231 and HCT-116 cancer cell lines, in particular 4-hydroxyphenylbenzamide derivative of 3-ethylquinazolinone 7d, which revealed IC50 of 5.39 ± 0.08 μM and 4.11 ± 0.13 μM, in comparison with IC50 of 29.13 ± 2.28 μM and 33.50 ± 2.43 μM, obtained for the reference drug, sorafenib, respectively...Whereas, It was approximately 1.26 times more potent than vorinostat against HDAC-2, demonstrating an IC50 of 0.363 ± 0.013 μM...Meanwhile, the expression level of caspase-3 and the BAX/BCL-2 ratio were markedly elevated in HCT-116 cells treated with 7d. Finally, the presented data are reliable for developing dual VEGFR-2 and HDAC inhibitors as anticancer drugs and reveal lead molecules for such purpose.

In this first real-world analysis of post-alloHCT FLT3-TKI maintenance in older adults, utilization was low and adherence was modest, although not impaired by age alone. Gilteritinib demonstrated the highest adherence and appeared to have favorable tolerability. Strategies to improve adherence and prospective data in older adults are needed to maximize the benefits of FLT3-TKI maintenance in this population.

IGF2BP3 knockdown increased ovarian cancer sensitivity to sorafenib. This study confirmed that IGF2BP3 knockdown inhibited ovarian cancer cell malignancy, promoted ferroptosis and inhibited autophagy-mediated EMC2 degradation, and verified that IGF2BP3 knockdown increased the sensitivity to sorafenib in ovarian cancer mice.

The miR-21/SASH1 axis play a critical role in sorafenib resistance in HBV-associated HCC, and targeting miR-21 may provide a promising therapeutic strategy to enhance treatment efficacy.

To rigorously validate this framework and overcome the limitations of public bulk datasets, we combined cross-cohort statistical benchmarking with original RNA-sequencing data generated from a laboratory-derived palbociclib-resistant model (MCF7-PR)...In application, the framework identified sorafenib as a top-ranked candidate for reversing CDK4/6i resistance... This study presents TIHS as a mechanism-agnostic, experimentally validated bridge between resistance-state transcriptomes and clinical decision-making. By coupling computational prioritization with in vitro functional verification, we demonstrate that targeting topology-defined hubs is a viable strategy for overcoming therapy resistance.