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From Genomic Insight to Clinical Impact: Dramatic Response in RET Fusion-positive Pancreatic Cancer.

Created on 02 Oct 2026

Authors

Jessica Lucchetti, Paola Cimini, Lorenzo Angotti, Giulia Barnini, Emanuela DI Giacomo, Luca Galbato Muscio, Daniele Nitti, Bruno Vincenzi, Giuseppe Tonini

Published in

Anticancer research. Volume 46. Issue 10. Pages 5751-5757.

Abstract

Pancreatic cancer remains one of the deadliest solid malignancies despite advances in systemic treatment. Outcomes with current therapies remain modest, with a 5-year overall survival rate of no more than 20%. Although rare, oncogenic RET fusions represent a clinically actionable alteration and may predict substantial benefit from selective RET inhibition.
A 48-year-old woman with pancreatic ductal adenocarcinoma developed liver metastases after first-line modified FOLFIRINOX. Comprehensive genomic profiling of the initial biopsy identified an NCOA4-RET fusion involving NCOA4 exon 6 and RET exon 12. Selpercatinib was initiated through a compassionate-use program at 160 mg twice daily. After approximately three months, the patient achieved a reduction of more than 50% in the sum of target-lesion diameters according to RECIST version 1.1. The response was sustained for more than 12 months despite dose reduction for persistent grade 2 hypertransaminasemia. The most recent assessment showed continued regression, including complete disappearance of some liver metastases. The patient remains clinically well, with an ECOG performance status of 0 and ongoing treatment.
This case demonstrates the potential for durable and clinically meaningful responses to RET-targeted therapy in RET fusion-positive pancreatic cancer. It also supports the use of comprehensive genomic profiling to identify rare but actionable molecular alterations in patients with advanced pancreatic cancer.

PMID:
42823154
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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