sorafenib

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.

P2/3, N=87, Not yet recruiting, Nanfang Hospital, Southern Medical University

FAM83A promotes MASH pathogenesis by interacting with RAF1 to activate ERK signaling, thereby stimulating fatty acid and cholesterol biosynthesis. Targeting this axis may offer therapeutic potential for MASH and metabolic dyslipidemia.

OS can be accurately predicted in patients with HCC receiving sorafenib by combining certain radiomics features with clinical metadata, centered primarily on baseline characteristics.

Collectively, our findings underscore the pivotal role of Sh/TgE in modulating drug particle size within CSD matrices through distinct mechanisms. Furthermore, our study underscores the potential of P188-mediated CSD formulations in augmenting the dissolution rate and bioavailability of poorly soluble drugs by minimizing drug particle size and sustaining drug supersaturation, thereby enhancing the efficacy of sorafenib in treating liver cancer.