P4, N=60, Active, not recruiting, Centre Hospitalier Universitaire de Nice | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Sep 2027 | Trial primary completion date: Mar 2025 --> Sep 2025

Three components (quercetin, oleic acid, tetrandrine) were highlighted as particularly effective...In conclusion, the therapeutic effect of the HL-RG combination against RCC is primarily mediated by its bioactive components, QUE, OA, and TET. These components regulate the HIF-1 signaling pathway, activating genes involved in the cellular response to hypoxia and modulating the expression of proteins that control glucose metabolism, cell proliferation, and angiogenesis.

Cisplatin resistance is a major contributor to treatment failure in ovarian cancer (OC). Molecular dynamics simulations demonstrated that hesperidin, cissamine and tetrandrine exhibited strong binding affinities toward AURKA, vitamin D receptor, and TTK. Future studies are encouraged to focus on the experimental validation of these compounds and delve deeper into the possible mechanisms of drug resistance, aiming to improve their therapeutic effectiveness and real-world applicability.

P3, N=132, Terminated, Mannkind Corporation | N=234 --> 132 | Trial completion date: Dec 2028 --> Nov 2025 | Recruiting --> Terminated | Trial primary completion date: Aug 2026 --> Nov 2025; Futility

MDR1 inhibitor verapamil and MDR1-targeted siRNA were used to evaluate the functional impact of LSR-induced MDR1. In contrast, knockout of LSR expression in MDA-MB-468 cells, which express higher levels of LSR, significantly sensitized the cells to doxorubicin-induced growth inhibition and apoptosis. Our data demonstrated that LSR overexpression promotes TNBC cell proliferation and invasion, and upregulation of MDR1 in these cells renders them resistant to doxorubicin, suggesting that targeting LSR could be a useful strategy to overcome chemoresistance in TNBC.

P=N/A, N=64, Not yet recruiting, Affiliated hangzhou first people's hospital, zhejiang university school of medicine; Hangzhou First People's Hospital

P=N/A, N=60, Not yet recruiting, The First Affiliated Hospital of Army Medical University (Southwest Hospital); The First Affiliated Hospital of Army Medical University (Southwest Hos

Drug screening further indicated that resistant cells maintained under irinotecan pressure exhibited a multidrug-resistant phenotype, while withdrawn cells regained sensitivity, particularly to tyrosine kinase inhibitors. Supplementation with the efflux inhibitor Elacridar partially restored drug sensitivity in resistant cells, emphasizing the role of transporter-mediated efflux in maintaining resistance.

Verapamil assays confirmed reduced efflux liability for compounds 8 and 13. Compound 8 also showed a positive therapeutic index. These findings support rational design to mitigate efflux-mediated resistance.

Histopathological findings further verify the superiority of Lf-miRNA-126-Tet@ANPs. These results highlight Lf-miRNA-126-Tet@ANPs as a promising nanoplatform for chemo-gene targeted delivery against lung cancer.

P-gp and CD146 represent complementary markers of endothelial identity in gliomas and may serve as histopathological indicators of BBB integrity and tumor vascular remodeling. Their combined evaluation offers a novel insight into the BBB-BBTB transition and may support microvascular phenotyping as an adjunct criterion for glioma grading.

Notably, compound 15 demonstrated significant antiproliferative activity against all tested cell lines, with IC50 values ranging from 3.28 to 6.16 µM, which is superior to the first-line clinical drug 5-fluorouracil. With its remarkable antitumor activity, excellent synthetic process characteristics, and clear apoptosis-inducing mechanism, compound 15 has emerged as a highly promising clinical candidate. This C-7 modification platform provides a viable path for transforming natural product derivatives into clinical therapies for HCC treatment.