Imatinib

證據等級: L5

預測適應症: 10 個

Imatinib: From Chronic Myeloid Leukaemia/GIST to Fibroblastic Neoplasm (Dermatofibrosarcoma Protuberans)

One-Sentence Summary

Imatinib is a BCR-ABL/KIT/PDGFR tyrosine kinase inhibitor historically developed for chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST); detailed original indication text and MOA documentation are not present in this evidence pack (see Data Gaps DG001/DG002). Among 10 TxGNN-predicted indications screened for this drug, Fibroblastic Neoplasm — which the evidence maps clinically to Dermatofibrosarcoma Protuberans (DFSP) — has by far the strongest support, with 1 completed Phase 2 trial and 20 related publications, including a 2025 European interdisciplinary treatment guideline. Note that the single highest TxGNN score in this pack ("heart fibrosarcoma") has almost no corroborating evidence and is flagged Hold; it is discussed separately below.

Quick Overview

Item	Content
Original Indication	Not available in this evidence pack (drug.original_indications is empty; regulatory license text unavailable — DG001)
Predicted New Indication	Fibroblastic Neoplasm (clinically corresponds to Dermatofibrosarcoma Protuberans, DFSP)
TxGNN Prediction Score	99.94% (rank 1108 among all TxGNN candidate diseases; rank 2 of 10 in this evidence pack)
Evidence Level	L2
Germany Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available for imatinib in this evidence pack (Data Gap DG002). Based on generally known pharmacology, imatinib is a small-molecule inhibitor of BCR-ABL, KIT and PDGFR tyrosine kinases, and its efficacy in CML and GIST is well established.

For the "Fibroblastic Neoplasm" prediction, the evidence pack's own mechanistic rationale is clear and specific: this disease category corresponds substantially to DFSP, which carries a characteristic t(17;22)(q22;q13) COL1A1–PDGFB translocation leading to constitutive PDGFRB activation. This is a textbook molecular target for imatinib, and the mechanism-to-indication link is direct rather than inferred — DFSP with fibrosarcomatous transformation has in fact already been treated with imatinib in real-world oncology practice.

By contrast, the top-scored candidate by raw TxGNN score alone, "heart fibrosarcoma," has only a single 2008 drug-bulletin commentary as support, whose title explicitly states the evidence is "not robust." This illustrates why TxGNN score rank and evidence strength must be evaluated separately — see the full candidate screening table at the end of this report.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00085475	Phase 2	Completed	17	Imatinib in locally advanced/metastatic DFSP and giant cell fibroblastoma harboring the COL1A1/PDGFB fusion; trial directly enrolled molecularly-confirmed patients (Evidence Grade A).

Literature Evidence

PMID	Year	Type	Journal	Key Findings
39904126	2025	Review/Guideline	Eur J Cancer	European interdisciplinary (EADO/EDF/UEMS/EADV) updated guideline on DFSP diagnosis and treatment.
41236573	2025	Preclinical	Human Cell	Establishment of an imatinib-resistant DFSP cell line (DFSP-DPH1) for resistance research.
37610680	2023	Preclinical	Human Cell	Multi-omic profiling and ex vivo modeling of imatinib-resistant DFSP with fibrosarcomatous transformation.
36630365	2023	Review	Clin Exp Dermatol	Overview of DFSP clinical features, histology, and PDGFB-COL1A1 fusion (>90% of cases).
36999599	2023	Review	J Surg Oncol	Surgical management of DFSP; notes imatinib use in advanced/unresectable disease.
33993132	2021	Review	Curr Opin Otolaryngol Head Neck Surg	Diagnosis, workup, and treatment strategies for DFSP.
30297237	2018	Review	Bull Cancer	DFSP management; identifies t(17;22)(q22;q13) COL1A1/PDGFB as specific diagnostic marker.
31466588	2019	Review	Dermatol Clin	DFSP clinical/histologic characterization; radiation and systemic therapy in unresectable cases.
28795284	2017	Review	Curr Treat Options Oncol	Multidisciplinary treatment approach to DFSP.
26027711	2015	Review	Expert Rev Anticancer Ther	Current treatment options for DFSP; PDGF autocrine/paracrine mechanism.

Germany Market Information

Imatinib is currently not marketed in this jurisdiction (market_status: 未上市), and no product authorization records are present in this evidence pack (total_licenses: 0). Regulatory approval and product listing data will need to be sourced separately if repurposing is pursued.

Cytotoxicity

Imatinib's original indications (CML, Ph+ ALL, GIST) place it within the antineoplastic drug category, though it acts as a targeted therapy rather than a conventional cytotoxic agent.

Item	Content
Cytotoxicity Classification	Targeted therapy (BCR-ABL/KIT/PDGFR tyrosine kinase inhibitor) — based on known drug class; not derived from evidence-pack toxicity data
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Please refer to the package insert warnings and precautions
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Please refer to the package insert for safety information. No key warnings, contraindications, or drug–drug interaction data were available in this evidence pack (flagged as Data Gap DG001, severity: Blocking, currently preventing S1 safety evaluation).

Full Screening Summary of All Predicted Indications

For completeness, all 10 TxGNN candidates in this evidence pack are ranked below by evidence quality rather than raw score, since the two frequently diverge:

Rank (by score)	Disease	TxGNN Score	Evidence Level	Decision Stage	Recommendation	Note
2	Fibroblastic Neoplasm (≈DFSP)	99.94%	L2	S3	Proceed with Guardrails	Strongest signal; PDGFB fusion, direct Phase 2 trial
3	Conventional Fibrosarcoma	99.93%	L2	S2	Proceed with Guardrails	Evidence largely overlaps with DFSP; true "conventional" fibrosarcoma lacks PDGFR/KIT driver data — needs molecular subtyping before use
6	Liposarcoma	99.88%	L2	S2	Research Question	Mixed Phase 2 evidence; unselected populations show limited response; needs PDGFR/KIT-enriched subgroup
1	Heart Fibrosarcoma	99.94%	L4	S0	Hold	Highest raw score but only 1 non-robust 2008 commentary
4	Kidney Fibrosarcoma	99.93%	L4	S1	Research Question	Basket trial only; literature match appears to be a keyword mismatch (FSGS, unrelated renal disease)
5	Low Grade Fibromyxoid Sarcoma	99.93%	L5	S0	Hold	Wrong driver gene (FUS-CREB3L2); literature is an unrelated case series
7	Liver Fibrosarcoma	99.86%	L5	S0	Hold	No trials or literature at all
8	Familial Mediterranean Fever	99.86%	L5	S0	Hold	No plausible mechanistic link; likely knowledge-graph false positive
9	Ovarian Myxoid Liposarcoma	99.85%	L5	S0	Hold	No supporting data
10	Familial Rhabdoid Tumor	99.83%	L5	S0	Hold	Driven by SMARCB1 loss, unrelated to kinase inhibition

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The single well-supported signal in this evidence pack is Fibroblastic Neoplasm/DFSP, backed by a completed Phase 2 trial with a molecularly-defined population (COL1A1-PDGFB fusion) and a 2025 clinical guideline. All other 9 candidates are either weakly supported (L4) or effectively unsupported model artifacts (L5) and should be held pending stronger evidence.

To proceed, the following is needed:

TFDA/regulatory label data (warnings, contraindications) — currently a Blocking gap (DG001) preventing initial safety screening (S1)
Formal MOA documentation from DrugBank (DG002)
Molecular confirmation protocol (COL1A1-PDGFB testing) to define the target subpopulation for Fibroblastic Neoplasm/Conventional Fibrosarcoma indications
For Liposarcoma: PDGFR/KIT expression-based patient enrichment strategy before further evaluation
Regulatory pathway assessment, since the drug is not currently marketed in this jurisdiction (0 authorizations)
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.