P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting

Furthermore, CDDO-Me did not compromise the antitumor efficacy of DOX/LAP in breast cancer cells. CDDO-Me protects against DOX/LAP-induced cardiotoxicity by stabilizing GPX4 and inhibiting ferroptosis, offering a promising therapeutic strategy that preserves cardiac function without interfering with chemotherapy.

These findings identify Niclosamide as a potent dual STAT1/STAT3 inhibitor capable of reversing IFN-γ- and hypoxia-driven immune evasion. Repurposing Niclosamide may represent a promising strategy to enhance the efficacy of immune checkpoint blockade in solid tumors.

Notably, 8 exhibited significant antitumor efficacy comparable to CDDO-Me (bardoxolone methyl), which had entered clinical trials. Taken together, 8 represents a promising candidate for the treatment of cancer and merits further study.

TAMs enhanced the proliferation, invasion, and migration of PC3 cells, but these effects were suppressed by the STAT3 inhibitor WP1066 and IL-6 neutralizing antibodies...IL-6 increased the activation of JAK2 and STAT3 proteins in PC3 cells, which was reduced by both treatments. These findings underscore the role of TAMs in promoting prostate cancer progression through IL-6-mediated JAK2/STAT3 signaling, suggesting the potential of targeting this pathway as a therapeutic strategy for advanced prostate cancer.

P1, N=132, Terminated, Vividion Therapeutics, Inc. | Trial completion date: Jan 2027 --> Dec 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Dec 2025; The study has ended

Molecular docking analyses supported the binding of CUR and DOX to key ferroptosis regulators. This study shows the potential of CUR to sensitize DOX-resistant cancer cells through ferroptosis-linked-oxidative stress targeting.

The findings herein demonstrated that mitochondrial uncouplers inhibit MSCP through FTO-dependent m6A demethylation. This work identified mitochondrial uncoupling as a novel and promising therapeutic approach for promoting m6A demethylation and targeting MSCP in metastatic breast cancer.

P4, N=100, Not yet recruiting, Tongji Hospital

Pharmacological inhibition of the TNF signaling pathway with R-7050 completely abolished the synergistic efficacy of RT/TMZ/ACT001. Taken together, our results demonstrate that ACT001 combined with RT/TMZ can overcome the immunosuppressive barrier of GBM to achieve immune cure in GBM via TNF-CXCL10-CD8+ signaling, strongly suggesting the priority of combining ACT001 with RT/TMZ rather than with αPD-1 in clinical trials.

Importantly, either the knockdown of MDM4 or pharmacological inhibition of JAK2/STAT3 signaling pathway with JSI-124 partially attenuated MTX-induced ferroptosis, improved renal function indicators, and attenuated histopathological damage in vivo. Our findings demonstrate that MTX mediates phosphorylation-dependent activation of the JAK2/STAT3 pathway, which facilitates MDM4/MDM2 interaction to induce ferroptosis-associated nephrotoxicity. These findings support a role for JAK2/STAT3-MDM4/MDM2 signaling in MTX-induced ferroptosis and suggest that targeted inhibition of this axis may represent a potential nephroprotective strategy.

P1/2, N=32, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China