Brain metastasis from KRAS wild-type pancreatic cancer and organoid correlates: a case report

Background: Although pancreatic cancer is an aggressive malignancy with a propensity for metastatic spread, brain metastases (BrMs) remain exceptionally rare (<1% incidence). Case Description: We present a case of BrMs in a 69-year-old pancreatic cancer patient. This patient initially presented with a history of chronic pancreatitis, abdominal and back pain, and significant weight loss. After the diagnostic biopsy confirmed pancreatic cancer, the patient was enrolled onto the PASS-01 clinical trial and was treated with standard of care chemotherapy before progressing and developing BrMs 10 months after cancer diagnosis. The BrMs were removed via craniotomy, and the patient also underwent radiation and chemotherapy before enrolling onto the MYTHIC clinical trial for PKMYT1 inhibitor, RP-6306. Successful generation of a BrM-derived organoid line enabled high-throughput drug screening, which recapitulated the patient's clinical resistance to standard therapies [gemcitabine/nab-paclitaxel, 5-fluorouracil (5-FU)], and showed sensitivity to afatinib, everolimus and RMC-6236. Conclusions: wild-type pancreatic cancer with atypical amplifications is likely to exhibit unique metastatic tropisms. Finally, we suggest that patient-derived organoids pharmacotyping can mirror clinical drug responses and help evaluate therapeutic avenues for patient treatment.