sorafenib

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and the available targeted therapies (e.g., sorafenib, lenvatinib) have limited options and frequent drug resistance. These compounds synergize with conventional targeted agents to overcome drug resistance through direct cytotoxicity or targeting hypertrophic lysosomal drug release. This article reviews the regulation of LDCD and the role of natural products in HCC based on PubMed, Web of Science and CNKI databases, aiming to providing a reference for the treatment of drug-resistant liver cancer.

Treatment by CM in combination with SB could decrease neoplastic features in HCC group. The hepatic expression of Bcl2 was decreased, and the release of cytosolic cathepsin B was increased in the combination group. Also, the hepatic concentration of Beclin-1 decreased in the combination group and there was autophagosome accumulation in transmission electron microscope (TEM). The results indicate that the concomitant use of CM and SB may be considered a possible new therapeutic option in managing HCC by targeting the cathepsin B/Bcl2/Beclin-1 pathway.

SRF@Au@M NPs were fabricated through the size optimization of MIL-100(Fe), sorafenib (SRF) loading, in-situ growth of Au nanoparticles (Au NPs) and surface modification with dihydrolipoic acid derivatives...Consequently, the SRF@Au@M NPs triggered a potent ferroptosis storm in 4T1 tumor cells and achieved an 92.5% tumor growth inhibition in tumor-bearing mice, significantly higher than that of other treatment groups. Our sophisticated strategy based on CRNs provides a new promising paradigm for ferroptosis activation and cancer treatment.

NOX4 emerges as a key regulator of the STAD inflammatory microenvironment and a robust prognostic biomarker. Its role in immune modulation and chemoresistance provides novel insights for developing precision therapeutic strategies in STAD.

Clinically, the concurrent overexpression of SHC4 and FTH1 has been identified as a potential prognostic marker for poor outcomes in patients with hepatocellular carcinoma. Collectively, our study demonstrates the pivotal role of SHC4 in regulating ferroptosis in hepatocellular carcinoma and highlights its potential as a novel therapeutic target for overcoming sorafenib resistance.

Here we focus on three mechanistically complementary drugs-sorafenib, cisplatin, and olaparib-because each converges, directly or indirectly, on the redox/LPO axis (system xc-/GPX4 modulation, mitochondrial ROS, and SLC7A11 regulation, respectively), modulating tumor cell responses by inducing PUFA oxidation, mitochondrial dysfunction, and membrane damage. Among regulated cell death modalities, ferroptosis is strictly dependent on lipid peroxidation, whereas apoptosis, necrosis, necroptosis, pyroptosis, and immunogenic cell death can be modulated by lipid peroxidation but do not universally require it. Collectively, these mechanisms indicate that lipid peroxidation is an important-though not exclusive-determinant of anticancer drug sensitivity and resistance, and that its dual, context-dependent role (tumor-suppressive at high flux, tumor-promoting under chronic, sub-lethal exposure) must be considered when designing LPO-based therapeutic strategies.

High‑risk patients exhibited reduced sorafenib sensitivity (higher IC50), and sorafenib treatment downregulated APOH, SPP1, and VTN but not SLCO2A1. We established a robust ARG‑based prognostic signature for HCC that improves risk stratification and highlights links between angiogenesis, immune microenvironment, and drug response.

Mechanistically, ISO inhibited the phosphorylation of ERK1/2, p38 and JNK, all of which contribute to ferroptosis suppression. These findings provide evidence that chronic stress‑induced ADRB2 activation promotes sorafenib resistance by mitigating ferroptotic cell death.

Oral azacitidine (CC-486) demonstrated overall survival benefit in older patients in first complete remission who were not transplant candidates, establishing a standard of care in this population. In FLT3-mutated AML, post-transplant maintenance with sorafenib and gilteritinib reduces relapse risk, with emerging evidence supporting MRD as a predictive biomarker for benefit. Other targeted agents and immunotherapies have shown promising early-phase results, although confirmatory data are limited. Ongoing phase III studies will clarify optimal patient selection, treatment duration, and integration with transplantation, aiming to transform post-remission management from passive surveillance to precision-based relapse prevention.

Ponatinib emerged as the top-ranked computational candidate (mean: - 10.07 kcal/mol), followed by Regorafenib (- 9.64), Sorafenib (- 9.46), and Entrectinib (- 9.45), while non-oncology drugs including antrafenine, betrixaban, and maraviroc demonstrated novel multi-target binding profiles...MM-GBSA calculations revealed a binding hierarchy concordant with docking scores (R2 = 0.92): Ponatinib-VEGFR2 (ΔGbind = - 42.38 kcal/mol) > Entrectinib-CDK6 (- 38.56) > Ponatinib-EGFR (- 33.24) > Entrectinib-HER2 (- 28.47) > Dacomitinib-HDAC3 (- 24.63 kcal/mol)...As the present study is entirely computational, the identified compounds should be regarded as hypothesis generating leads requiring experimental validation through in vitro kinase and HDAC3 inhibition assays, cell based studies, and target engagement confirmation before any translational conclusions can be drawn. The online version contains supplementary material available at 10.1007/s40203-026-00681-w.

Multiomics confirmed modulation of apoptosis, inflammation, oxidative stress, and metabolic pathways. SF potentiates a promising anti-HCC therapeutic efficacy of SB.

Moreover, treatment of HepG2 cells with S-MLPs led to a 12.99-fold increase in the activity of apoptotic proteins and decreased production of angiogenic proteins from 331.57 to 83.34 pg mL-1. The R2 relaxation value of 57.262 mM-1 s-1 obtained for the MLPs, indicating their high potential for clinical cancer management.