Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward
<i>RET</i> alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung cancer (NSCLC). Multikinase inhibitors (MKIs) with anti-<i>RET</i> activities resulted in variable efficacy with significant toxicities because of low targe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Journal of Molecular Pathology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-5261/3/1/3 |
| _version_ | 1797470353948147712 |
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| author | Maria Lucia Reale Valentina Bertaglia Angela Listì Silvia Novello Francesco Passiglia |
| author_facet | Maria Lucia Reale Valentina Bertaglia Angela Listì Silvia Novello Francesco Passiglia |
| author_sort | Maria Lucia Reale |
| collection | DOAJ |
| description | <i>RET</i> alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung cancer (NSCLC). Multikinase inhibitors (MKIs) with anti-<i>RET</i> activities resulted in variable efficacy with significant toxicities because of low target specificity. Selective RET kinase inhibitors, such as pralsetinib and selepercatinib, demonstrated high efficacy and favorable tolerability in advanced <i>RET</i>-rearranged NSCLC patients, leading to their introduction in the clinical setting. Among the different approaches available for the identification of <i>RET</i> rearrangements, next-generation sequencing (NGS) assays present substantial advantages in terms of turnaround time and diagnostic accuracy, even if potentially limited by accessibility issues. The recent advent of novel effective targeted therapies raises several questions regarding the emergence of resistance mechanisms and the potential ways to prevent/overcome them. In this review, we discuss molecular testing and treatment strategies to manage <i>RET</i> fusion positive NSCLC patients with a focus on resistance mechanisms and future perspectives in this rapidly evolving scenario. |
| first_indexed | 2024-03-09T19:35:22Z |
| format | Article |
| id | doaj.art-331756b27c6c46a3b5b75552dcdc9764 |
| institution | Directory Open Access Journal |
| issn | 2673-5261 |
| language | English |
| last_indexed | 2024-03-09T19:35:22Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Molecular Pathology |
| spelling | doaj.art-331756b27c6c46a3b5b75552dcdc97642023-11-24T01:56:08ZengMDPI AGJournal of Molecular Pathology2673-52612022-01-0131243710.3390/jmp3010003Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look ForwardMaria Lucia Reale0Valentina Bertaglia1Angela Listì2Silvia Novello3Francesco Passiglia4Department of Oncology, S. Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, ItalyDepartment of Oncology, S. Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, ItalyDepartment of Oncology, S. Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, ItalyDepartment of Oncology, S. Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, ItalyDepartment of Oncology, S. Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano, Italy<i>RET</i> alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung cancer (NSCLC). Multikinase inhibitors (MKIs) with anti-<i>RET</i> activities resulted in variable efficacy with significant toxicities because of low target specificity. Selective RET kinase inhibitors, such as pralsetinib and selepercatinib, demonstrated high efficacy and favorable tolerability in advanced <i>RET</i>-rearranged NSCLC patients, leading to their introduction in the clinical setting. Among the different approaches available for the identification of <i>RET</i> rearrangements, next-generation sequencing (NGS) assays present substantial advantages in terms of turnaround time and diagnostic accuracy, even if potentially limited by accessibility issues. The recent advent of novel effective targeted therapies raises several questions regarding the emergence of resistance mechanisms and the potential ways to prevent/overcome them. In this review, we discuss molecular testing and treatment strategies to manage <i>RET</i> fusion positive NSCLC patients with a focus on resistance mechanisms and future perspectives in this rapidly evolving scenario.https://www.mdpi.com/2673-5261/3/1/3<i>RET</i>NSCLCselpercatinibpralsetinibnext-generation sequencingacquired resistance |
| spellingShingle | Maria Lucia Reale Valentina Bertaglia Angela Listì Silvia Novello Francesco Passiglia Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward Journal of Molecular Pathology <i>RET</i> NSCLC selpercatinib pralsetinib next-generation sequencing acquired resistance |
| title | Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward |
| title_full | Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward |
| title_fullStr | Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward |
| title_full_unstemmed | Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward |
| title_short | Molecular Testing and Treatment Strategies in <i>RET</i>-Rearranged NSCLC Patients: Stay on Target to Look Forward |
| title_sort | molecular testing and treatment strategies in i ret i rearranged nsclc patients stay on target to look forward |
| topic | <i>RET</i> NSCLC selpercatinib pralsetinib next-generation sequencing acquired resistance |
| url | https://www.mdpi.com/2673-5261/3/1/3 |
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