FAP theranostics as a pan-cancer stromal strategy

Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.

Rather than finding a different target for each cancer, this idea hits the cancer-associated fibroblasts that almost all solid tumours share. FAP-targeted alpha or beta radioligands such as FAP-2286 would be given to FAPI-PET-avid pancreatic, gastric and sarcoma patients irrespective of tumour-cell genotype, delivering radiation to the stroma with crossfire into adjacent tumour cells and depleting the fibroblasts that exclude T cells. Stroma is genetically stable, so resistance mutations are not expected. The test is phase 2 FAP-2286 cohorts selected by FAPI PET, with paired biopsies and a PD-1 combination in pancreatic cancer. At early-clinical maturity it addresses the bottleneck Cold tumours and the immunosuppressive microenvironment.

Confidence

25% to 50%likelyNuclide editors (initial estimate), 2026-09-07 · Imaging is convincing; therapeutic dosimetry to stroma is the unknown.

Hypothesis

FAP-targeted alpha or beta radioligands produce disease control in FAPI-PET-avid pancreatic, gastric, and sarcoma patients irrespective of tumour-cell genotype, and sensitise to immunotherapy by depleting immunosuppressive fibroblasts.

Rationale

Stroma is genetically stable (no resistance mutations); crossfire range of 177Lu (2 mm) covers adjacent tumour cells; CAF depletion relieves T-cell exclusion.

Proposed test

Phase 2 FAP-2286 cohorts with FAPI PET selection and paired biopsies for CAF depletion and T-cell infiltration; combination with PD-1 in pancreatic cancer.

Maturity

early clinical