Temsirolimus
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Temsirolimus: From Renal Cell Carcinoma to Liposarcoma
One-Sentence Summary
Temsirolimus is an mTOR inhibitor originally approved for the treatment of renal cell carcinoma (RCC). The TxGNN model predicts it may also be effective for Liposarcoma, with 5 clinical trials (2 using temsirolimus/Torisel directly) and 1 publication currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Renal cell carcinoma (RCC) — not present in the local regulatory dataset, but consistently referenced across the supporting clinical/literature evidence as the approved indication |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.54% |
| Evidence Level | L2 |
| EU Market Status | Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not present in the structured drug record (flagged as a High-severity data gap). However, across the supporting clinical trial and literature evidence, Temsirolimus is consistently described as a selective inhibitor of mTORC1 (mammalian target of rapamycin complex 1), which blocks the PI3K/AKT/mTOR signaling pathway. This pathway is one of the central drivers of cell growth, proliferation, and survival, and Temsirolimus is approved for metastatic renal cell carcinoma, where dysregulated mTOR/HIF signaling drives tumor progression.
Liposarcoma — particularly the dedifferentiated subtype — frequently shows activation of the same PI3K/AKT/mTOR pathway. This shared molecular vulnerability is the mechanistic basis for repurposing mTOR-pathway inhibitors into soft-tissue sarcoma treatment. Multiple drugs in the same rapalog/mTOR-inhibitor class (sirolimus, everolimus, ridaforolimus) have already been tested in liposarcoma and related sarcoma subtypes, and Temsirolimus itself (as Torisel) has direct clinical evidence in advanced soft-tissue and bone sarcoma populations, reinforcing the biological plausibility of the TxGNN prediction.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01614795 | Phase 2 | Completed | 46 | Cixutumumab + temsirolimus in pediatric recurrent/refractory sarcoma; direct temsirolimus evidence (Grade A) |
| NCT00949325 | Phase 1/2 | Completed | 24 | Torisel (temsirolimus) + liposomal doxorubicin in advanced soft tissue and bone sarcoma; dose-finding and efficacy assessment (Grade A, direct evidence) |
| NCT02821507 | Phase 2 | Completed | 70 | Sirolimus (parent compound, not temsirolimus) + cyclophosphamide in metastatic/unresectable myxoid liposarcoma and chondrosarcoma; mTOR inhibition prevented tumor growth in preclinical models (Grade B, class-effect evidence) |
| NCT03114527 | Phase 2 | Active, not recruiting | 48 | Ribociclib + everolimus (mTOR inhibitor class, not temsirolimus) in advanced dedifferentiated liposarcoma and leiomyosarcoma (Grade B, class-effect evidence) |
| NCT00093080 | Phase 2 | Completed | 216 | Ridaforolimus (mTOR inhibitor, AP23573) monotherapy in advanced sarcoma (Grade B, class-effect evidence) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20497911 | 2010 | Review | Bulletin du cancer | Review of targeted treatment strategies for rare connective tissue tumors and sarcomas, including mTOR-pathway-directed therapies relevant to liposarcoma subtypes |
EU Market Information
No EU marketing authorization is currently on record for Temsirolimus in this dataset (0 authorizations, market status: not marketed). This should be confirmed against the EMA product register, since Temsirolimus (Torisel) has historically held EU authorization for renal cell carcinoma and mantle cell lymphoma.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy — mTOR inhibitor (rapalog class) |
| Myelosuppression Risk | Please refer to the SmPC warnings and precautions |
| Emetogenicity Classification | Please refer to the SmPC warnings and precautions |
| Monitoring Items | Please refer to the SmPC warnings and precautions |
| Handling Protection | Please refer to the SmPC warnings and precautions |
Safety Considerations
Please refer to the SmPC for safety information.
Note: A case report (PMID 24830996) describes bowel perforation associated with temsirolimus use in a recently irradiated patient with uterine leiomyosarcoma — this is a safety signal from the broader evidence set, not a confirmed contraindication, and should be reviewed alongside the official SmPC.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Temsirolimus has direct clinical evidence (Torisel) in advanced soft-tissue and bone sarcoma populations, and mechanistically plausible class-effect evidence from other mTOR inhibitors specifically in liposarcoma. However, no trial to date has tested temsirolimus specifically and exclusively in a liposarcoma-confirmed cohort, and key safety/regulatory data are still missing.
To proceed, the following is needed:
- TFDA/EMA package insert warnings and contraindications (currently a Blocking data gap — required before any S1 safety assessment)
- Formal mechanism of action (MOA) documentation from DrugBank or equivalent source
- Confirmation of current EU marketing authorization status (dataset shows 0 licenses / not marketed, which should be reconciled with EMA records)
- A liposarcoma-subtype-specific trial or expanded-access data, since existing direct temsirolimus evidence is in mixed sarcoma populations rather than liposarcoma alone
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.