sorafenib

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.

P2, N=10, Completed, HonorHealth Research Institute | Active, not recruiting --> Completed

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.

Further literature review and feasibility assessment narrowed the list to six candidates: malonaldehyde, mercaptoethanol, glycine, para-chlorophenol, methoxyamine, and ethanolamine. These findings support YBX1 as a promising therapeutic target in hepatocellular carcinoma and demonstrate the utility of drug repurposing to rapidly identify candidate inhibitors. Targeting YBX1 may provide a viable strategy for enhancing treatment efficacy and overcoming sorafenib resistance in advanced HCC.

Genetic disruption of CAPRIN1 restores NCOA4 expression and resensitizes resistant tumors to sorafenib. Our work establishes SG activity as a prognostic biomarker and reveals a druggable SG-ferroptosis axis, offering novel strategies to overcome therapy resistance in HCC.

Knockdown of EFEMP1 promotes ferroptosis by inactivating PI3K/AKT to resensitize sorafenib-resistant HCC cells to sorafenib.

Metabolomic analyses of various TKIs identified convergent signatures along three interconnected axes: (1) mitochondrial bioenergetic dysfunction characterized by impaired long-chain fatty acid oxidation and adenylate depletion; (2) disruption of endothelial nitric oxide signaling with redox imbalance, including increased nitrotyrosine, Nox activation, and eNOS uncoupling; and (3) an inflammatory metabolic profile marked by elevated branched-chain and aromatic amino acids, creatine, and osmolytes. Rodent models of sunitinib and sorafenib replicate these signatures and demonstrate histological injury, contractile dysfunction, and fibrosis. Preclinical intervention data, particularly restoration of myocardial carnitine, AMPK signaling, and fatty acid oxidation by L-carnitine, provide proof of concept for metabolomics-guided cardioprotection. Metabolomics can identify mechanistic biomarkers that facilitate the early detection, risk stratification, and targeted prevention of TKI-induced cardiovascular injury. Translation into precision cardio-oncology requires prospective validation, standardized assays, and biomarker-driven interventional trials.

We identified a purinergic prognostic signature in HCC and demonstrated that the combination therapy of sorafenib and doxazosin targets the adenosine pathway and specific receptors. We show that the stromal microenvironment sustains CD73 protein expression even under transcriptional inhibition, highlighting the critical role of 3D co-culture models in deciphering therapeutic resistance mechanisms.