P2, N=48, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

By enabling automated analysis of FRET images, FRET-SAM significantly enhances the efficiency and accuracy of FRET two-hybrid assays, while eliminating subjective bias. The capability of FRET-SAM to resolve drug-target interactions establishes it as a promising tool for drug discovery.

P1/2, N=74, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

These effects are mediated through the NRP2/NF-κB/TNFα axis, which also underlies NRP2-induced sorafenib resistance. Targeting this axis with the TNF-α inhibitor adalimumab effectively reversed sorafenib resistance in ccRCC, suggesting a promising therapeutic strategy.

Cabozantinib is recommended after sorafenib failure in systemic therapy of hepatocellular carcinoma (HCC), based on the results of CELESTIAL...In CLERANCE, tolerability and efficacy of cabozantinib were similar to those observed in CELESTIAL. We obtained more details in the management of cabozantinib doses, identified surrogate markers of better outcome, and underlined prolonged overall survival for patients able to undergo subsequent lines.

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.

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).