sorafenib

This study established a prognostic model based on seven MGs in PLC, correlating them with patient prognosis and Sor treatment response, and provided preliminary evidence that G6PD and KIF20A may promote PLC progression through the IL‑17/AKT/STAT3 pathway.

At a functional level, cells grown in stiffer matrix demonstrated augmented proliferation and chemoresistance to cisplatin and sorafenib with nuclear translocation of NRF2. Multiplex imaging of human HCC tissues confirmed that collagen-rich regions co-localize with high KEAP1 and TOM20 expression, confirming the in vitro findings. This study demonstrates ECM stiffness to be a bioactive material property that guides mitochondrial and redox networks through KEAP1 signaling, and the mechanically tunable collagen platforms to be of a utility for dissection and manipulation of tumor adaptation mechanisms.

Screening of candidate compounds revealed that treatment with ML162, RSL3, and sorafenib resulted in maximum FRET efficiencies (EDmax) of 0.492, 0.483, and 0.503, respectively-significantly lower than that of control cells (0.548)-indicating effective disruption of USP8/GPX4 binding. This study successfully establishes a novel and efficient FRET-based drug screening model for targeting ferroptosis.

Knockdown of ELK1 or LINC00839 exerted synergistic roles with Erastin or ferroptosis-inducing chemotherapeutic drug Sorafenib to enhance ferroptosis, thereby delaying tumor growth in vivo. In summary, this study reveals that ELK1-mediated transcription activation of LINC00839 promotes ferroptosis resistance of NPC cells by destabilizing RCHY1 mRNA and subsequent repressing DJ-1 ubiquitination and degradation. These findings provide potential therapeutic targets for overcoming ferroptosis resistance in NPC.

P3, N=450, Active, not recruiting, University of Birmingham | Trial completion date: Aug 2027 --> Dec 2027 | Trial primary completion date: Aug 2026 --> Dec 2026

Huh7 cells were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions, treated with sorafenib alone or combined with PI3K inhibitor LY294002. Our findings suggest that hypoxia reduces the sensitivity of HCC cells to sorafenib, and that GRB2 contributes to this process through activation of the PI3K/AKT pathway. Targeting GRB2 may represent a potential strategy to enhance sorafenib efficacy in HCC treatment under hypoxic conditions.

Among the designed series, Compounds 2h and 2l were the most potent derivatives across both tumor models, exhibiting IC50 values of 23.3 and 30.9 μM (HCT-116), respectively, and 31.5 and 39.2 μM (MCF-7), respectively, compared to sorafenib (IC50 = 8.8 and 11.6 μM, respectively)...Additionally, Compound 2h markedly suppressed immunomodulatory proteins TNF-α and IL-6 levels by 80.9% and 88.2%, respectively, in comparison to dexamethasone (82.7% and 93.2%, respectively), which attenuates tumor-promoting inflammation, disrupting pro-survival signaling pathways and metastasis. In silico ADMET, toxicity, and molecular docking studies were performed; notably, the docking simulations generated an interesting hypothesis for potential direct binding to Bcl-2, an effect distinct from the experimentally observed downstream downregulation of its expression. The present results pave the way for further developing of 2h candidate as a multi-tyrosine kinases inhibitor toward colon cancer cells.

Upon reaching the tumor tissue through specific targeting, the nanovaccines disassemble within the tumor cells, releasing the Fenton reaction catalyst ferrous iron (Fe2+), the system Xc- inhibitor sorafenib (SRF), and necroptosis inducer shikonin...Collectively, our findings present a cancer immunotherapy strategy that exploits dual ferroptosis and necroptosis induction to trigger ICD, bypassing the limitations of apoptosis-dependent pathways. This strategy coordinates with the STING pathway to achieve potent antitumor immunity, providing a promising paradigm for HCC treatment, and offering a promising and translatable path for clinical development.

Elevated plasma IL-8 levels are strongly associated with poor outcomes in patients with advanced HCC undergoing TKI treatment, suggesting a potential role for IL-8 in guiding TKI therapeutic decisions and identifying high-risk patients.

Current therapies, including tyrosine kinase inhibitors such as sorafenib and lenvatinib, modestly extend survival, and treatments that combine the use of antiangiogenic agents and immune checkpoint inhibitors (ICIs) have yet to prolong median overall survival beyond two years. In both subcutaneous and orthotopic allograft models, the combination of LNDPPA and an anti-PD-1 antibody enhanced CD8+ T cells recruitment and function and exhibited superior tumor growth inhibition compared to the conventional sorafenib plus an anti-PD-1 antibody. These findings suggest that LNDPPA, particularly in combination with an ICI, holds promise as a potent therapeutic strategy for uHCC, and also provide insight into the development of multi-targeted combination therapies for other tumor types.

The phase 3 REFLECT study (NCT01761266) established lenvatinib's noninferiority to sorafenib for unresectable hepatocellular carcinoma (uHCC). This analysis highlights the importance of tumor reduction and AFP response as predictors of survival outcomes in lenvatinib-treated patients with uHCC. These data continue to support lenvatinib as an effective first-line treatment option.

Several multikinase blockers targeting RET have been approved by the FDA for the treatment of cancer: (i) vandetanib for medullary thyroid carcinoma and (ii) cabozantinib, lenvatinib, and sorafenib for differentiated thyroid cancer. Pralsetinib is a specific RET blocker that is FDA-approved for the treatment of medullary thyroid cancer, RET-fusion positive thyroid cancer and NSCLC. Selpercatinib is FDA-approved for the management of RET-mutant medullary thyroid cancer, RET-fusion-positive thyroid cancer, and other RET-fusion-positive solid tumors...Currently, the number of new cases of thyroid cancer bearing RET mutations or RET-fusion proteins is about 13,000 per year and the number of cases of RET-driven NSCLC range from about 2000-4000 per year in the United States. Inactivating RET mutations result in Hirschsprung disease, a congenital disorder leading to aganglionosis of the gastrointestinal tract.