temsirolimus

P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P1, N=45, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Unknown status --> Completed

P2, N=65, Not yet recruiting, Rapa Therapeutics LLC | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Mar 2028 --> Mar 2029

P2, N=67, Not yet recruiting, Yonsei University

P2, N=720, Recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jan 2026 --> Dec 2026

P1, N=38, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P=N/A, N=20, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2028

Drug sensitivity predictions indicated patients with high MPO expression were more sensitive to PI3K/AKT inhibitors (e.g., temsirolimus), but their TIDE score suggested a potentially lower response to immunotherapy...MPO serves as an independent prognostic marker and its downregulation contributes to tumor growth via PI3K/AKT signaling while influencing the immune microenvironment. These findings suggest MPO as a new target for combined therapeutic strategies based on metabolic intervention.

P3, N=325, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

Single-agent neratinib has limited activity in ERBB2-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients.

In this study, we established chemoresistant uveal melanoma cell lines by exposing parental cells to dacarbazine, cisplatin, or gemcitabine and performed high-throughput drug screening incorporating normal human epidermal melanocytes (NHEMs) as a normal control to assess both efficacy and selectivity. Our screening identified temsirolimus and selumetinib as top candidates, with temsirolimus exhibiting strong tumor-selective cytotoxicity...Mechanistically, temsirolimus downregulated mammalian target of rapamycin (mTOR) signaling, as indicated by reduced p-mTOR, p-S6, and p-4EBP1 expression in tumor tissues. These findings demonstrate that temsirolimus selectively targets chemoresistant uveal melanoma cells, enhances chemotherapy efficacy, and suppresses tumor growth via mTOR inhibition, supporting its potential clinical application as a novel therapeutic strategy for chemoresistant uveal melanoma.

Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki-2 cells, indicating 2.83- and 1.2-fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN-38 compared with Caki-2 cells. Notably, etoposide, 5-fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types...A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP-binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells.