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Lorlatinib Induces Durable Disease Stabilization in a Pancreatic Cancer Patient with a ROS1 p.L1950F Mutation: Case
Janna-Lisa Velthaus1, Peter Iglauer2, Ronald Simon2
1Department of Hematology, Oncology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, j.velthaus@uke.de.
Introduction:
The prognosis of pancreatic cancer has improved only modestly in recent years. This is partly due to the lack of development in precision oncology including immune oncology in this entity. Rearrangements of the proto-oncogene tyrosine protein kinase ROS1 gene represent driver alterations found especially in lung cancer. Tyrosine kinase inhibitors (TKI) with activity against ROS1 including lorlatinib substantially improved the outcome of this patient population. Anecdotal evidence reports treatment of pancreatic cancer harboring ROS1 fusions with ROS1 TKI, but data concerning treatment of patients with ROS1 point mutations are lacking.
Case Presentation:
This case describes a pancreatic cancer patient harboring a ROS1 point mutation that occurred without an underlying ROS1 rearrangement and thus not in the resistance situation. The heavily pretreated patient showed a strong decrease of the tumor biomarkers (CA19-9 and CEA) and radiologically a durable stable disease to the targeted treatment with lorlatinib, thereby achieving a progression-free survival of 12 months.
Conclusion:
Our data are the first to show a clinical benefit from targeted treatment with ROS1 TKI in a cancer patient with a thus far undescribed ROS1 point mutation without a concomitant ROS1 rearrangement. Furthermore, they indicate that ROS1 could be an oncogenic driver in pancreatic cancer. This subgroup could be eligible for targeted treatments, which may contribute to the urgently needed improvement in patient outcome.
Insights
Targeted therapy with lorlatinib showed a clinical benefit in a pancreatic cancer patient with a ROS1 point mutation. This finding suggests ROS1 as a potential oncogenic driver, offering new treatment avenues for pancreatic cancer.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Pancreatic cancer prognosis remains poor due to limited progress in precision oncology.
- ROS1 gene alterations, particularly rearrangements, are known drivers in lung cancer, responsive to tyrosine kinase inhibitors (TKIs).
- Limited data exists on ROS1 alterations in pancreatic cancer, especially point mutations.
Observation:
- A pancreatic cancer patient presented with a ROS1 point mutation, not a rearrangement.
- The patient was heavily pretreated and received targeted therapy with lorlatinib.
- Tumor biomarkers (CA19-9, CEA) decreased, and radiological scans showed durable stable disease.
Findings:
- This case is the first to demonstrate clinical benefit from ROS1 TKI treatment in a pancreatic cancer patient with a novel ROS1 point mutation without a concurrent rearrangement.
- The patient achieved a 12-month progression-free survival.
Implications:
- The findings suggest ROS1 may act as an oncogenic driver in a subset of pancreatic cancers.
- This subgroup of patients may benefit from targeted ROS1 TKI therapy.
- Targeted treatments could significantly improve outcomes for pancreatic cancer patients.
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