sorafenib

Among the tested compounds, 7a demonstrated the most potent activity, with IC₅₀ values ranging from 3.98 to 9.67 μM, comparable with doxorubicin...It also markedly inhibited EGFR and VEGFR-2 with IC₅₀ values of 1.67 and 6.72 μM, compared to Erlotinib and Sorafenib, respectively...Molecular docking studies confirmed the strong binding affinity of 7a within the active sites of both EGFR and VEGFR-2, supporting its proposed mechanism of action. These findings position compound 7a as a promising lead for further development as a dual EGFR/VEGFR-2-targeting anticancer agent, particularly for aggressive cancers such as TNBC.

In xenograft and spontaneous models, combined HBO-TKIs treatment delays tumor progression and modulates the HNF4A/RCN1 axis. Taken together, our findings elucidate a hitherto uncharacterized role of HBO in regulating ER-mitochondria calcium homeostasis and support its clinical application as an adjunctive therapy in TKI-resistant HCC.

In conclusion, KA7 exhibits strong anticancer properties, inducing apoptosis, arresting the G1 cell cycle, stimulating autophagy, and displaying positive immunomodulatory effects. According to these results, KA7 is a promising lead chemical for additional preclinical testing as a potent sorafenib substitute.

Oncofetal reprogramming-based prognostic signature robustly stratifies HCC patient survival across independent cohorts. DUSP9 is identified as a core oncofetal regulator that drives stem-like traits in HCC. Mechanistically, DUSP9 suppresses ERK1/2-phosphorylation, stabilizes PPARG, and transcriptionally activates SCD. The DUSP9-ERK1/2-PPARG-SCD axis remodels lipid metabolism to support proliferation, cell mobility, and sorafenib resistance.

P3, N=837, Active, not recruiting, Exelixis | Trial completion date: Dec 2024 --> Jul 2026

CXCR6 antagonism with SBI-457 can modulate β-catenin activation and may help overcome sorafenib resistance in selected HCC models. These findings support further development of CXCR6 antagonists as single agents or combination therapies to improve treatment outcomes in HCC.

Importantly, inhibition of LPA-Arf6-mediated EV macropinocytosis significantly improves the sorafenib efficacy. Our findings uncover a previously unrecognized mechanism mediated by differential TME and CD147⁺ EV macropinocytosis in HCC and highlight the LPA-Arf6-macropinocytosis as a novel targeting axis to overcome SFR in HCC.

The detection of GNAQ/GNA11 mutations in ctDNA at baseline was associated with an inferior outcome. (ClinicalTrials.gov: NCT01377025).

Conversely, the high-risk group exhibited distinct genomic features and was predicted to be more sensitive to specific targeted agents, including Navitoclax and Sorafenib. We identified and validated a novel 7-gene prognostic signature derived from a subpopulation of EGFR-TKI-resistant macrophages. This signature accurately predicts patient survival, offers insights into the molecular mechanisms of therapy resistance in HCC, and provides a promising tool for improved patient stratification and the development of personalized treatment strategies.

In this study, 8 SUMO-ylation related prognostic genes were identified in BRCA, namely GPC1, CAPZA1, NUDCD1, MTDH, COX7A1, PLK3, FAM43A and CEBPD, offering fresh perspectives on the prognosis of BRCA.

Post-HCT azacitidine may have a role for MRD-positive AML. In AML with FLT3-internal tandem duplication mutation, post-HCT gilteritinib and sorafenib can be evidence-based strategies to target MRD. In ALL, blinatumomab is a powerful tool to eradicate MRD in patients with Philadelphia (Ph)-positive or Ph-negative ALL; tyrosine kinase inhibitors are indicated for post-HCT management of Ph+ ALL. Despite these advances, the optimal duration and type of intervention still remain unknown for many patients with acute leukemia who have peri-HCT MRD.

AntiHCC assay suggested 19 analogues showed better inhibitory activity than sorafenib on HepG2, SK-Hep-1, and Huh7 cells...In vivo, dimer 10 at 30 and 60 mg/kg inhibited tumor weight up to 64 % and 69 % without detectable toxicity, and IHC analysis confirmed in vivo target engagement. This study identified compound 10 as a potential antiHCC agent targeting CDK2, and warrants further investigation.