Stivarga (regorafenib)

We confirmed that Regorafenib disrupts this entire axis and, in combination with anti-PD-1 therapy in ATC, overcomes immunosuppression to elicit potent anti-tumor immunity. Our studies revealed the GPI/O-GlcNAcylation/THBS1 signal as a master regulator of myeloid cell crosstalk and established a novel therapeutic strategy for targeting this metabolic checkpoint to potentiate ATC immunotherapy.

In zebrafish MASLD-HCC, PRS-OPT-nominated dosing reduced hepatic macrophage accumulation and improved disease-relevant transcriptional and morphological readouts. PRS-OPT enables interpretable, multi-objective dose nomination for MASLD-relevant HCC contexts, and establishes PRS-OPT as an interpretable, multi-objective framework for regimen nomination that is directly extensible to additional phenotypic endpoints for preclinical evaluation.

P2, N=31, Completed, The First Affiliated Hospital of Zhengzhou University

In vitro, these compounds outperformed sorafenib and regorafenib, inducing stronger p53-mediated cell-cycle arrest, autophagy, apoptosis, and reduced invasiveness via JNK/c-Jun pathways. In vivo study performed with 21-day treatment of SET135 or SET171 showed superior anti-tumor effects compared to sorafenib via apoptotic mechanisms in HCC-transplanted mice. These findings highlight JNK-IN-5A derivatives as promising HCC therapeutic candidates capable of inducing both apoptotic and necrotic cell death.

Additionally, in bilateral tumor models, PE-RR could boost the therapeutic efficacy of PD-1 checkpoint blockade, increase the generation of anti-tumor immune memory and minimize the low responsiveness of immune checkpoint inhibitors in liver cancer. The stable Pickering embolic emulsion offers an innovative approach for the clinical translation of embolization therapy.

In this MAIC analysis, soto960+pani demonstrated statistically significant improvement in response rates and OS in patients with chemorefractory KRAS G12C-mutated mCRC.

P2, N=214, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Trial completion date: Mar 2026 --> Jun 2026

Differentially methylated region analysis suggested that resistance to regorafenib may involve disruptions in WNT signaling, cadherin-mediated adhesion, and presenilin pathways. These findings highlight the potential of DNA methylation profiling in guiding therapeutic strategies and warrant further validation in clinical settings.

Agents such as trifluridine/tipiracil, regorafenib, and fruquintinib offer additional benefit in heavily pretreated mCRC. Anticipated paradigm shifts with novel agents may further refine management strategies and improve outcomes for these patients. As the landscape evolves, ongoing multidisciplinary collaboration will be essential in optimizing both patient selection and therapy sequencing as new options become available.

P2, N=60, Recruiting, National Cancer Institute, Naples

Our predictive model may help identify patients at high risk of early mortality after regorafenib or trifluridine/tipiracil initiation and support shared decision-making between clinicians and patients regarding further chemotherapy or best supportive care.

In contrast, macrophage-conditioned medium had little effect on regorafenib and increased sensitivity to dabrafenib, suggesting that resistance depends on the inhibitory profile of each drug. The multi-kinase inhibitor masitinib-which targets several kinases along this resistance network-strongly restored sensitivity to trametinib and RMC-6236. Together, these data define a macrophage-driven resistance network in KRAS-mutant colorectal cancer organoids and support combined inhibition of RAS-pathway and tyrosine kinase signalling.