Selpercatinib for RET-positive advanced pancreatic cancer detected by liquid biopsy: a case-based insight

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis and limited effective treatments. Standard chemotherapy offers modest survival benefits, and actionable genetic alterations are rare. RET gene fusions occur in less than 1% of PDAC cases but present a potential target for therapy. We describe a case of a 62-year-old woman with metastatic PDAC who progressed on two lines of chemotherapy. A RET fusion (TPR - RET) was identified via liquid biopsy and confirmed on tissue biopsy. Treatment with the selective RET inhibitor selpercatinib led to rapid symptom improvement, normalization of tumor markers, and significant tumor regression. A partial radiographic response of approximately 60% was achieved, with manageable toxicity. This case highlights the importance of comprehensive molecular profiling, including noninvasive methods like liquid biopsy, in identifying rare but actionable mutations. Emerging evidence from clinical trials supports the efficacy of RET inhibitors in RET-altered PDAC. Broader integration of genomic testing in PDAC may uncover new therapeutic opportunities and improve patient outcomes.