Hallmarks of RET and Co-occuring Genomic Alterations in RET-aberrant Cancers
Autor: | Aakash Desai, Vivek Subbiah, Jason Roszik, Jacob J. Adashek, Gilbert J. Cote, Alexander Y. Andreev-Drakhlin |
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Rok vydání: | 2021 |
Předmět: |
congenital
hereditary and neonatal diseases and abnormalities endocrine system Cancer Research Oncogene Proteins Fusion endocrine system diseases medicine.medical_treatment Biology medicine.disease_cause Article Acquired resistance Neoplasms medicine Animals Humans Rearranged during transfection Protein Kinase Inhibitors neoplasms Kinase Egfr inhibition Proto-Oncogene Proteins c-ret Immunotherapy Phenotype Oncology Mutation Cancer research Carcinogenesis |
Zdroj: | Mol Cancer Ther |
ISSN: | 1538-8514 1535-7163 |
Popis: | Activating receptor-tyrosine kinase rearranged during transfection (RET) mutations and fusions are potent drivers of oncogenesis. The recent FDA approvals of highly potent and selective RET inhibitors, selpercatinib and pralsetinib, has altered the therapeutic management of RET aberrant tumors. There is ample evidence of the role of RET signaling in certain cancers. RET aberrations as fusions or mutations occur in multiple cancers, however, there is considerable phenotypic diversity. There is emerging data on the lack of responsiveness of immunotherapy in RET-altered cancers. Herein, we review the registrational data from the selective RET-inhibitor trials, and comprehensively explore RET alterations in pan-cancer adult malignancies and their co-alterations. These co-occuring alterations may define the future of RET inhibition from specific selective targeting to customized combination therapies as data are rapidly emerging on both on-target and off-target acquired resistance mechanisms. Fascinatingly, oncogenic RET fusions have been reported to mediate resistance to EGFR inhibition and KRASG12C inhibition. |
Databáze: | OpenAIRE |
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