{"entity":{"id":"idea-fap-theranostics-pancancer","kind":"idea","name":"FAP theranostics as a pan-cancer stromal strategy","aka":[],"tldr":"Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.","summary":"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.","asOf":"2026-09-04","links":[{"label":"Kratochwil et al., 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer (Journal of Nuclear Medicine 2019)","url":"https://doi.org/10.2967/jnumed.119.227967"}],"tags":[],"related":[],"cancers":["pancreatic","gastric","sarcoma"],"sections":[],"technologies":["fapi-pet","radioligand-therapy","targeted-alpha-therapy"],"targets":["fap"],"drugs":["fap-2286"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07219238"],"people":[],"bottlenecks":[],"keyPapers":["paper-kratochwil-j-nucl-med"],"journals":[],"dependsOn":[],"notes":[],"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.","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"},"route":"/ideas/idea-fap-theranostics-pancancer/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"fapi-pet","kind":"technology","name":"FAPI PET","route":"/technologies/fapi-pet/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"}],"drug":[{"id":"fap-2286","kind":"drug","name":"FAP-2286 (177Lu / 68Ga)","route":"/drugs/fap-2286/"}],"trial":[{"id":"nct07219238","kind":"trial","name":"Study to Evaluate the Diagnostic Performance of GEH300079 (68Ga) Injection PET/CT for Detection of PC in Patients With Colorectal, Gastric, Ovarian, o","route":"/trials/nct07219238/"}],"paper":[{"id":"paper-kratochwil-j-nucl-med","kind":"paper","name":"68 Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer","route":"/key-papers/paper-kratochwil-j-nucl-med/"}],"idea":[{"id":"idea-fund-academic-radiopharma-pipeline","kind":"idea","name":"A university cyclotron network with shared regulatory files for new tracers","route":"/ideas/idea-fund-academic-radiopharma-pipeline/"},{"id":"idea-pdac-stromal-reprogramming-not-depletion","kind":"idea","name":"Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint","route":"/ideas/idea-pdac-stromal-reprogramming-not-depletion/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}]}}