ideasIdea

Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)

Small-cell lung cancer is at least four diseases under the microscope's uniform appearance. Treat each by its transcription-factor subtype.

Rudin/Gay classification: SCLC-A (ASCL1, DLL3-high, BCL-2 dependent), SCLC-N (NEUROD1, Aurora kinase dependent), SCLC-P (POU2F3, PARP/nucleoside dependent), SCLC-I (inflamed, immunotherapy-responsive). Retrospective IMpower133 analysis suggested SCLC-I gains most from atezolizumab.

Hypothesis

Prospective subtype assignment (RNA or IHC) will predict benefit: DLL3 engagers in SCLC-A, immunotherapy in SCLC-I, Aurora kinase inhibitors in SCLC-N, and PARP/ATR inhibitors in SCLC-P.

Rationale

Subtype-specific dependencies are reproducible in cell lines and PDX; DLL3 expression tracks ASCL1.

What would test it

Biomarker-stratified umbrella trial assigning relapsed patients by IHC subtype to tarlatamab, ATR inhibitor, Aurora A inhibitor, or chemo-immunotherapy.

Maturity

preclinical evidence

Connected

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not linked directly; found by shared links

Pairing
Sequencing DLL3 engager and B7-H3 ADC in relapsed SCLC
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Trial
DeLLphi-304
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Trial
DeLLphi-305
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Product
Rovalpituzumab tesirine
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Idea
Detect tumours changing cell type from RNA in the blood
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Institution
Hospital Universitario 12 de Octubre
Shares DLL3, Tarlatamab, Small-cell lung cancer.
Person
Se-Hoon Lee
Shares Tarlatamab, Small-cell lung cancer.
Pathway
Notch signalling
Shares DLL3, Tarlatamab, Small-cell lung cancer.

Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)

Connected

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cancers

targets

drugs