temsirolimus

Overview

Rapamycin-ester mTOR inhibitor; used in pediatric sarcoma trial regimens (e.g., ARST0431).

Evidence in the corpus

• Used in ARST0431-era chemotherapy regimens during the 2000–2021 MSKCC extremity rhabdomyosarcoma cohort window PMID:37315267.
• PI3K/AKT/mTOR pathway altered in ~28% of clear cell renal cell carcinoma (CCRCC) tumors; authors cite prior temsirolimus trials in advanced RCC as context for therapeutic targeting of this pathway PMID:23792563.
• Combined with H3B-8800, temsirolimus (mTOR inhibitor) showed synergistic activity in SF3B1-mutant/del(13q) CLL cells in vitro (IC50 2.148 μM in DM vs 0.0001055 μM in Mdr-only) and in vivo (median OS 9→27 days in DM CLL NSG mice, 3-fold improvement, P<0.01); human CLL patient samples with both lesions were preferentially sensitive to the combination PMID:26200345.
• Authors note prior efficacy of temsirolimus in leiomyosarcoma alongside everolimus, but flag the limitation of compensatory AKT activation and recommend evaluating dual TORC1/TORC2 inhibitors given the pervasive AKT-pathway alterations in LMS PMID:29100075

Resistance mechanisms

• Not reported in corpus.

Cancer types (linked)

• RMS, ARMS, CLLSLL

Sources

• PMID:37315267
• PMID:23792563 — TCGA CCRCC comprehensive molecular characterization; PI3K/AKT/mTOR pathway altered in ~28% of tumors, with temsirolimus trials in advanced RCC cited as therapeutic context.
• PMID:26200345 — SF3B1-mutant/del(13q) CLL mouse model; temsirolimus + H3B-8800 combination synergistic in DM CLL cells in vitro and in vivo.

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