Torisel (temsirolimus)

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.

In conclusion, temsirolimus therapy had a significantly positive effect on survival in patients with mRCC. Patients treated with temsirolimus showed significantly longer median survival and median PFS compared to patients treated with IFN-alpha.

This study revealed the heterogeneity of metabolic molecules in KIRP and established a prognostic machine learning model that enhances risk stratification and may optimize chemotherapy strategies in the management of KIRP.

Immune-related pathways were enriched in high-risk patients, and drug sensitivity analysis indicated that high-risk patients were more responsive to sunitinib and temsirolimus. IL2RG and its related 6-IRLs are potential biomarkers for ccRCC progression. The 6-IRLs model provides a robust tool for predicting prognosis and guiding therapeutic decisions.

This investigation thoroughly uncovered the significance of PPP1R14B in HCC, and established a PPP1R14B-linked immune prognostic signature. The findings facilitate the classification of HCC patients into distinct cohorts for developing individualized therapeutic approaches.

While eleven compounds (aldosterone, arecoline, bortezomib, dasatinib, decitabine, dexamethasone, erlotinib, everolimus, gefitinib, temsirolimus, and thalidomide) either had no effect on median lifespan or were toxic, five compounds (all-trans retinoic acid, berberine, fisetin, propranolol, and ritonavir) extended lifespan in Caenorhabditis elegans . Evolutionary conservation of retinoic acid as a signaling ligand and the structure of the downstream effector network of retinoic acid combine to suggest that the all-trans retinoic acid pathway is an ancient metabolic regulatory system that can modulate lifespan. Our results highlight the potential of combining computational prediction of longevity interventions with the power of nematode functional genetics and underscore that the manipulation of a conserved metabolic regulatory circuit by co-opting endogenous signaling molecules is a powerful approach for discovering aging interventions.

Rapamycin, Everolimus, Temsirolimus and Other ATP-competitive inhibitors work by binding to the mTOR protein and preventing it from activating downstream signaling pathways that control cell growth and division. These findings highlight the potential of Rapa-PLGA NPs to enhance Rapamycin's therapeutic efficacy by integrating nanotechnology-driven delivery with gene regulatory mechanisms. This nanoparticle-based system presents a promising strategy for improving targeted bladder cancer therapy and overcoming drug resistance, warranting further in vivo investigation.

Natural compounds derived from a novel vegetable oil blend demonstrate promising molecular interactions with key biomarkers of cervical carcinoma. These findings support their potential role as effective therapeutic agents and warrant further in vitro and in vivo validation.