P1, N=20, Active, not recruiting, Sohag University

This study investigates the characterization and biological effects of Dual Drug-Loaded Nanoparticles on HepG2/doxorubicin (DOX) cells, focusing on the anti-cancer ability of Doxorubicin/Curcumin-Polyethylene Glycol-Polycaprolactone Nanoparticles (DOX/Cur-PEG-PCL-NPs)...These results demonstrate that DOX/Cur-PEG-PCL-NPs effectively reverse chemoresistance and suppress tumor progression through modulation of the Nrf2 pathway and apoptosis induction, offering a promising strategy for targeted liver cancer therapy. The online version contains supplementary material available at 10.1007/s10616-025-00855-y.

IQCE emerges as a novel oncogene-associated biomarker with significant diagnostic and prognostic utility, particularly in SKCM. It promotes an immunosuppressive TME and oncogenic signaling while being localized to malignant cells. Although associated with chemoresistance, the vulnerability of IQCE-high tumors to RITA offers a promising therapeutic strategy. IQCE represents a compelling target for precision oncology.

P1, N=12, Enrolling by invitation, Keystone Nano, Inc | Not yet recruiting --> Enrolling by invitation | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Jul 2026 --> Feb 2027

Treatments for advanced HCC include multikinase inhibitors (Sorafenib or Lenvatinib), with limited response rates and serious side effects, or immunotherapy applicable to a small fraction of patients. No toxicity was observed after repeated injections of XON9 in a non-human primate. XON9 represents a promising and selective immunotherapy against refractory HCC.

P1, N=46, Recruiting, SciTech Development, Inc. | Trial completion date: Nov 2025 --> May 2027 | Trial primary completion date: May 2025 --> Dec 2026

Moreover, TGX-221 represents a promising novel therapeutic candidate, while HS2ST1 serves as a potential prognostic biomarker. These findings collectively provide tools for risk stratification and targeted therapy, advancing precision oncology for WT.

P1, N=68, Completed, VA Office of Research and Development | Recruiting --> Completed | N=140 --> 68 | Trial completion date: May 2026 --> Jul 2025

Moreover, 6i demonstrated a promising safety profile in hERG assay. Taken together, our finding suggest that 6i may be a potential candidate for further in vivo investigation.

P1/2, N=148, Suspended, Primocure Pharma | Trial completion date: Nov 2025 --> Nov 2027 | Active, not recruiting --> Suspended | Trial primary completion date: Nov 2025 --> Nov 2027

P1, N=100, Not yet recruiting, APR Applied Pharma Research s.a.

In comparison to doxorubicin, the spiro 2-pyridine derivative 9b exhibited the highest anti-proliferative activity, demonstrating IC50 values of 6.89 ± 0.4 μM and 5.68 ± 0.3 μM against HepG-2 and Caco-2 cell lines, respectively, with nearly 2-fold increase in efficacy observed in Caco-2 cells...Compound 9b exhibited significant inhibitory activity against h-DHFR, with an IC50 value of 0.192 ± 0.011 μM, compared to methotrexate (IC50 = 0.191 ± 0.011 μM). Furthermore, compound 9b demonstrated EGFR inhibitory activity, with IC50 of 0.109 ± 0.005 μM, which is close to the inhibition observed with Lapatinib (IC50 = 0.044 ± 0.002 μM)...In addition, in silico metabolism prediction using SwissADME and BioTransformer tools revealed that compound 9b is a potential inhibitor of CYP2C9 and CYP3A4, and is predicted to undergo metabolic transformations primarily via aromatic hydroxylation and ketone reduction, while maintaining acceptable stability of its ester moiety. Finally, the molecular docking assessment, together with the direct in vitro enzymatic inhibition results, confirmed that the 2-pyridone derivative 9b can potently bind to and inhibit both EGFR and h-DHFR through favorable binding interactions.