Selinexor

證據等級: L5

預測適應症: 10 個

Selinexor: From an Undocumented Original Indication to Progesterone-Receptor Negative Breast Cancer

One-Sentence Summary

Selinexor (DrugBank DB11942) is an XPO1/CRM1 nuclear export inhibitor; its documented original indication is not available in this evidence pack, and the drug is not currently marketed in Denmark. The TxGNN model surfaced several breast-cancer-related predictions, but only Progesterone-Receptor Negative Breast Cancer is backed by an actual completed clinical trial — a small, investigator-initiated Phase 2 study (n=10) — while the model’s highest-scoring output (“drug-induced osteoporosis”) is flagged in the evidence pack itself as likely model noise with no supporting mechanism, trials, or literature.

Quick Overview

Item	Content
Original Indication	Not documented in this evidence pack (`original_indications` empty; not marketed in Denmark)
Predicted New Indication	Progesterone-Receptor Negative Breast Cancer
TxGNN Prediction Score	97.20%
Evidence Level	L2
Denmark Market Status	Not marketed
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for Selinexor is not available in the Laegemiddelstyrelsen registration record used to build this evidence pack (flagged as a High-severity data gap). Based on the analysis accompanying this prediction, Selinexor is understood to act as a selective inhibitor of nuclear export (SINE), targeting XPO1/CRM1. This forces tumour-suppressor proteins such as p53, FOXO3a and IκB to remain in the nucleus and reduces translation of oncoproteins such as MYC and cyclin D1 — a mechanism with preclinical support across multiple solid tumours, including breast cancer.

Progesterone-receptor negative breast cancer typically carries a poorer prognosis and responds less well to hormonal therapy. An XPO1-inhibition mechanism offers a non-hormone-dependent therapeutic rationale, which is consistent with why this candidate — among the model’s breast-cancer-related outputs — has actual clinical investigation behind it (see Clinical Trial Evidence below).

It is worth noting that this was not the model’s top-scoring output. The highest-ranked prediction, “drug-induced osteoporosis” (score 99.22%), is explicitly annotated in the evidence pack as lacking any bone-protective mechanism — Selinexor’s known adverse-effect profile (anorexia, weight loss, fatigue, thrombocytopenia) runs counter to such an indication — and has zero supporting trials or literature. Similarly, HER2-positive breast carcinoma, normal breast-like subtype, and PR-positive breast cancer show no direct mechanistic or clinical-trial support and appear to reflect generic “breast cancer” node proximity in the knowledge graph rather than subtype-specific signal. Progesterone-receptor negative breast cancer is therefore presented here as the most credible candidate, being the only one grounded in an actual completed trial.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02402764	Phase 2	Completed	10	Investigator-initiated, single-arm study of selinexor (KPT-330) in metastatic triple-negative breast cancer, assessing efficacy, safety and tolerability. Small sample size (n=10) limits statistical power; graded as exploratory rather than confirmatory evidence.

Literature Evidence

Currently no related literature available.

Denmark Market Information

Selinexor is not currently marketed in Denmark (Laegemiddelstyrelsen market status: Not marketed) and holds no national or centralised (EMA) marketing authorisations on record in this evidence pack.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (XPO1/CRM1 selective inhibitor of nuclear export, SINE)
Myelosuppression Risk	Signal noted in evidence-pack analysis: thrombocytopenia listed among Selinexor’s known safety issues; not yet confirmed against an official label
Emetogenicity Classification	Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions
Monitoring Items	Complete blood count (with attention to platelets), given the noted thrombocytopenia signal; liver and renal function
Handling Protection	Please refer to the Summary of Product Characteristics (SmPC) and institutional cytotoxic/hazardous-drug handling policy

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information — key warnings, contraindications and drug-drug interaction data are not yet available in this evidence pack (DDI query returned no results).

Note: the evidence pack’s analytical commentary (not verified against an official label) references known Selinexor-associated adverse effects — anorexia, weight loss, fatigue, and thrombocytopenia — relevant for future monitoring-plan design.

Conclusion and Next Steps

Decision: Hold

Rationale: The lead candidate (progesterone-receptor negative breast cancer) has a plausible mechanism and one completed but small, single-arm Phase 2 trial (L2, n=10) — a promising but early-stage signal. Progression is currently blocked by a Blocking-severity data gap (missing Danish/TFDA-equivalent label warnings and contraindications, which prevents even an initial safety screen) and a High-severity gap in documented mechanism of action. The model’s other, higher-scoring breast-cancer and osteoporosis predictions lack any clinical or mechanistic support and are assessed as likely model artifacts rather than genuine repurposing signals.

To proceed, the following is needed:

Official Danish/EU SmPC warnings, contraindications and DDI data for Selinexor (currently blocking initial safety screening)
Confirmed original indication and mechanism-of-action documentation from DrugBank or regulatory sources
Larger controlled (ideally randomized) trial data beyond the single-arm n=10 study before any guardrail-based progression is considered
Re-review of the other high-score, evidence-free predictions (drug-induced osteoporosis, HER2-positive breast carcinoma, normal breast-like subtype, PR-positive breast cancer) to confirm or formally reject them as model noise
Disclaimer

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