Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe
The incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers c...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1141314/full |
| _version_ | 1797834686629675008 |
|---|---|
| author | Rossella Elisei Enrique Grande Michael C. Kreissl Sophie Leboulleux Tarun Puri Nicolas Fasnacht Jaume Capdevila |
| author_facet | Rossella Elisei Enrique Grande Michael C. Kreissl Sophie Leboulleux Tarun Puri Nicolas Fasnacht Jaume Capdevila |
| author_sort | Rossella Elisei |
| collection | DOAJ |
| description | The incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers characteristic of each histologic subtype, such as differentiated thyroid cancer, including papillary, follicular, and medullary thyroid cancer. Oncogenic alterations identified include B-Raf proto-oncogene (BRAF) fusions and mutations, neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and rearranged during transfection (RET) receptor tyrosine kinase fusion and mutations. Multikinase inhibitors (MKIs) targeting RET in addition to multiple other kinases, such as sorafenib, lenvatinib and cabozantinib, have shown favourable activity in advanced radioiodine-refractory differentiated thyroid cancer or RET-altered medullary thyroid cancer; however, the clinical utility of MKI RET inhibition is limited by off-target toxicity resulting in high rates of dose reduction and drug discontinuation. Newer and selective RET inhibitors, selpercatinib and pralsetinib, have demonstrated potent efficacy and favourable toxicity profiles in clinical trials in the treatment of RET-driven advanced thyroid cancer and are now a therapeutic option in some clinical settings. Importantly, the optimal benefits of available specific targeted treatments for advanced RET-driven thyroid cancer require genetic testing. Prior to the initiation of systemic therapy, and in treatment-naïve patients, RET inhibitors may be offered as first-line therapy if a RET alteration is found, supported by a multidisciplinary team approach. |
| first_indexed | 2024-04-09T14:41:31Z |
| format | Article |
| id | doaj.art-a87bec9b601843c6addb293882d72dbe |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T14:41:31Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a87bec9b601843c6addb293882d72dbe2023-05-03T06:34:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11413141141314Current perspectives on the management of patients with advanced RET-driven thyroid cancer in EuropeRossella Elisei0Enrique Grande1Michael C. Kreissl2Sophie Leboulleux3Tarun Puri4Nicolas Fasnacht5Jaume Capdevila6Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyMedical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, SpainDivision of Nuclear Medicine, Department of Radiology and Nuclear Medicine, University Hospital of Magdeburg, Magdeburg, GermanyDepartment of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals, Geneva, SwitzerlandMedical Affairs, Eli Lilly and Company, Indianapolis, IN, United StatesMedical Affairs, Eli Lilly and Company, Indianapolis, IN, United StatesMedical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), IOBTeknon, Barcelona, SpainThe incidence of thyroid cancer is increasing worldwide with the disease burden in Europe second only to that in Asia. In the last several decades, molecular pathways central to the pathogenesis of thyroid cancer have revealed a spectrum of targetable kinases/kinase receptors and oncogenic drivers characteristic of each histologic subtype, such as differentiated thyroid cancer, including papillary, follicular, and medullary thyroid cancer. Oncogenic alterations identified include B-Raf proto-oncogene (BRAF) fusions and mutations, neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and rearranged during transfection (RET) receptor tyrosine kinase fusion and mutations. Multikinase inhibitors (MKIs) targeting RET in addition to multiple other kinases, such as sorafenib, lenvatinib and cabozantinib, have shown favourable activity in advanced radioiodine-refractory differentiated thyroid cancer or RET-altered medullary thyroid cancer; however, the clinical utility of MKI RET inhibition is limited by off-target toxicity resulting in high rates of dose reduction and drug discontinuation. Newer and selective RET inhibitors, selpercatinib and pralsetinib, have demonstrated potent efficacy and favourable toxicity profiles in clinical trials in the treatment of RET-driven advanced thyroid cancer and are now a therapeutic option in some clinical settings. Importantly, the optimal benefits of available specific targeted treatments for advanced RET-driven thyroid cancer require genetic testing. Prior to the initiation of systemic therapy, and in treatment-naïve patients, RET inhibitors may be offered as first-line therapy if a RET alteration is found, supported by a multidisciplinary team approach.https://www.frontiersin.org/articles/10.3389/fonc.2023.1141314/fullthyroid cancertyrosine kinase inhibitormedullary thyroid cancerpapillary thyroid cancerreceptor-tyrosine kinaseRET |
| spellingShingle | Rossella Elisei Enrique Grande Michael C. Kreissl Sophie Leboulleux Tarun Puri Nicolas Fasnacht Jaume Capdevila Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe Frontiers in Oncology thyroid cancer tyrosine kinase inhibitor medullary thyroid cancer papillary thyroid cancer receptor-tyrosine kinase RET |
| title | Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe |
| title_full | Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe |
| title_fullStr | Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe |
| title_full_unstemmed | Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe |
| title_short | Current perspectives on the management of patients with advanced RET-driven thyroid cancer in Europe |
| title_sort | current perspectives on the management of patients with advanced ret driven thyroid cancer in europe |
| topic | thyroid cancer tyrosine kinase inhibitor medullary thyroid cancer papillary thyroid cancer receptor-tyrosine kinase RET |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1141314/full |
| work_keys_str_mv | AT rossellaelisei currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope AT enriquegrande currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope AT michaelckreissl currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope AT sophieleboulleux currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope AT tarunpuri currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope AT nicolasfasnacht currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope AT jaumecapdevila currentperspectivesonthemanagementofpatientswithadvancedretdriventhyroidcancerineurope |