The activator RO8191 or inhibitor ruxolitinib of the JAK/STAT pathway was employed to confirm whether IKZF1 inhibited colon cancer development by regulating JAK2/STAT5 pathway...Furthermore, upregulation of IKZF1 promoted M1 macrophage polarization while inhibiting M2 macrophage polarization in vivo and in vitro by inhibiting the JAK2/STAT5 signaling pathway. This study identifies IKZF1 as a potential biomarker inactivating JAK2/STAT5 pathway for colon cancer.

Our results revealed that Rux-PCL-NPs, which increased the efficacy of ruxolitinib, regulated apoptosis and the JAK2/STAT5 pathway.

P3, N=218, Completed, Children's Oncology Group | Active, not recruiting --> Completed

This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.

Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested...Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer. Lestaurtinib is a novel inhibitor of ovarian cancer, including chemotherapy- and PARPi-resistant models, that acts through robust inhibition of the JAK/STAT pathway and synergizes with standard-of-care agents at clinically relevant concentrations.

The prediction of IC50 based on bioinformatics method indicated DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. In accordance with the prediction, cytotoxicity assay in DLBCL cell lines suggested the higher sensitivity to doxorubicin and gemcitabine in the high-risk group and the higher sensitivity to dasatinib in the low-risk group in DLBCL. The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

Therefore, pimozide could be a promising agent to support TKI therapies in ponatinib resistance. This research would help to clarify the role of cytokines in ponatinib resistance and advance the development of new therapeutics to utilize the STAT5 inhibitor pimozide in combination with TKIs.

This work demonstrated that cytosolic ssDNA accumulation promotes breast cancer immunogenicity and may be a novel therapeutic strategy to improve the efficacy of ICB with minimal toxicities.

Additionally, western blot analysis of compound 5h revealed inhibition of STAT3 and STAT5 phosphorylation at Tyr705 and Tyr694, respectively, with only a slight decrease in the total expression of STAT3 and STAT5 proteins. And lastly, molecular docking research provided additional insight on the 5h binding mechanism in the STAT3 and STAT5 SH2 domains.

Of two CDX and six clinical samples of OS and Ewing's sarcoma, DST identified proteasome inhibitors (bortezomib, carfilzomib) and CEP-701 as potentially effective drugs in common. This unique method of in vitro drug testing using 3D-cell cultures is feasible in surgically resected tissues of metastatic malignant bone tumors.

P3, N=218, Active, not recruiting, Children's Oncology Group | Trial completion date: Jul 2023 --> Jun 2024

Lestaurtinib treatment reduces tumor growth and increases mice survival. Our data indicate that Lestaurtinib produces in MB cells poly-pharmacological effects extending beyond the inhibition of its validated targets, supporting the possibility of repositioning this drug for MB treatment.