founder-mode-oncologylisted

# Founder Mode Oncology Systematic framework for navigating personalized cancer treatment, generalized from Sid Sijbrandij's osteosarcoma case (2022-2026). Transforms the ad-hoc "billionaire with a team" approach into a reproducible methodology using open-source tools and structured decision-making. ## The Three-Pillar Framework ### Pillar 1: Maximal Diagnostics Run every available diagnostic modality to build a complete molecular picture. Standard clinical panels miss non-obvious targets. **Minimum diagnostic stack (in priority order):** 1. **Genomics**: WGS + WES (tumor/normal paired) — somatic mutations, CNV, structural variants 2. **Transcriptomics**: Bulk RNA-seq + scRNA-seq (tumor + PBMCs) — gene expression, immune landscape, non-obvious targets 3. **Liquid biopsy**: ctDNA (tumor-informed, e.g. Signatera) + methylation-based (e.g. Northstar) — real-time monitoring 4. **Functional testing**: Organoid drug testing + mass response assays — empirical drug sensitivity 5. **Imaging**: Standard (CT/MRI) + novel PET tracers (68Ga-FAP, 68Ga-B7H3) — target validation 6. **Flow cytometry**: B/T cell subsets — immune status tracking **Critical insight**: scRNA-seq reveals targets that standard panels miss. In the reference case, scRNA-seq identified FAP overexpression in osteosarcoma — invisible to gene panels and WES — enabling the breakthrough radioligand therapy. **Tissue handling**: Always request cryopreserved (flash-frozen) samples alongside FFPE. FFPE destroys RNA qu