Version 1
: Received: 31 October 2021 / Approved: 2 November 2021 / Online: 2 November 2021 (22:19:36 CET)
How to cite:
Urbanska, E.M.; Sørensen, J.B.; Melchior, L.C.; Costa, J.C.; Santoni-Rugiu, E. Acquired Intergenic ANK3-RET Fusion as a Pralsetinib-Responsive Mechanism of Resistance to Osimertinib in EGFR-Mutated NSCLC. Preprints2021, 2021110052. https://doi.org/10.20944/preprints202111.0052.v1
Urbanska, E.M.; Sørensen, J.B.; Melchior, L.C.; Costa, J.C.; Santoni-Rugiu, E. Acquired Intergenic ANK3-RET Fusion as a Pralsetinib-Responsive Mechanism of Resistance to Osimertinib in EGFR-Mutated NSCLC. Preprints 2021, 2021110052. https://doi.org/10.20944/preprints202111.0052.v1
Urbanska, E.M.; Sørensen, J.B.; Melchior, L.C.; Costa, J.C.; Santoni-Rugiu, E. Acquired Intergenic ANK3-RET Fusion as a Pralsetinib-Responsive Mechanism of Resistance to Osimertinib in EGFR-Mutated NSCLC. Preprints2021, 2021110052. https://doi.org/10.20944/preprints202111.0052.v1
APA Style
Urbanska, E.M., Sørensen, J.B., Melchior, L.C., Costa, J.C., & Santoni-Rugiu, E. (2021). Acquired Intergenic ANK3-RET Fusion as a Pralsetinib-Responsive Mechanism of Resistance to Osimertinib in EGFR-Mutated NSCLC. Preprints. https://doi.org/10.20944/preprints202111.0052.v1
Chicago/Turabian Style
Urbanska, E.M., Junia Cardoso Costa and Eric Santoni-Rugiu. 2021 "Acquired Intergenic ANK3-RET Fusion as a Pralsetinib-Responsive Mechanism of Resistance to Osimertinib in EGFR-Mutated NSCLC" Preprints. https://doi.org/10.20944/preprints202111.0052.v1
Abstract
The unavoidable progression of EGFR-mutated NSCLC on EGFR-TKIs forces us to discover solutions for further therapies. Herein, we discuss the necessity of accurate genomic mapping of progressive disease illustrated by a patient case. Tumor rebiopsies at progression are strongly needed to characterize acquired resistance to EGFR-TKI. The necessary data, however, may be reliably obtained only by deep targeted next generation sequencing (NGS) of both DNA and RNA. The reported case is a patient with EGFR-mutant NSCLC, who progressed during second line Osimertinib with subsequent targeted treatment determined by the detection of an acquired intergenic ANK3-RET-fusion with concomitant PTEN-mutation and MDM2-amplification. These three acquired gene alterations represent potential mechanisms of TKI-resistance, not previously reported on second line Osimertinib. Yet, while PTEN-mutations and MDM2-amplification are currently undruggable, the ANK3-RET fusion allowed further personalized treatment by combining continuation of Osimertinib with the RET-TKI Pralsetinib, which resulted in objective partial response, so far for 7 months, and significant clinical improvement. Hence, complementary DNA- and RNA-based targeted NGS may be of importance in clinical routine to better reveal the current molecular state of the disease and contribute to the identification of further targeted therapy strategies. Indeed, further cases with acquired RET-fusions, including ANK3-RET, should be investigated to fully determine the effectiveness of RET-TKI-Osimertinib combinations.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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