RET fusions in solid tumors.

RET fusions in solid tumors.

Publication date: Dec 01, 2019

The RET proto-oncogene has been well-studied. RET is involved in many different physiological and developmental functions. When altered, RET mutations influence disease in a variety of organ systems from Hirschsprung’s disease and multiple endocrine neoplasia 2 (MEN2) to papillary thyroid carcinoma (PTC) and non-small cell lung cancer (NSCLC). Changes in RET expression have been discovered in 30-70% of invasive breast cancers and 50-60% of pancreatic ductal adenocarcinomas in addition to colorectal adenocarcinoma, melanoma, small cell lung cancer, neuroblastoma, and small intestine neuroendocrine tumors. RET mutations have been associated with tumor proliferation, invasion, and migration. RET fusions or rearrangements are somatic juxtapositions of 5′ sequences from other genes with 3′ RET sequences encoding tyrosine kinase. RET rearrangements occur in approximately 2.5-73% of sporadic PTC and 1-3% of NSCLC patients. The most common RET fusions are CDCC6-RET and NCOA4-RET in PTC and KIF5B-RET in NSCLC. Tyrosine kinase inhibitors are drugs that target kinases such as RET in RET-driven (RET-mutation or RET-fusion-positive) disease. Multikinase inhibitors (MKI) target various kinases and other receptors. Several MKIs are FDA-approved for cancer therapy (sunitinib, sorafenib, vandetanib, cabozantinib, regorafenib, ponatinib, lenvatinib, alectinib) and non-oncologic disease (nintedanib). Selective RET inhibitor drugs LOXO-292 (selpercatinib) and BLU-667 (pralsetinib) are also undergoing phase I/II and I clinical trials, respectively, with preliminary results demonstrating partial response and low incidence of serious adverse events. RET fusions provide a viable therapeutic target for oncologic treatment, and further study is warranted into the prevalence and pathogenesis of RET fusions as well as development of current and new tyrosine kinase inhibitors.

Li, A.Y., McCusker, M.G., Russo, A., Scilla, K.A., Gittens, A., Arensmeyer, K., Mehra, R., , Adamo, and Rolfo, C. RET fusions in solid tumors. 24988. 2019 Cancer Treat Rev (81):

Concepts Keywords
Adenocarcinomas Chemistry
Breast ROS1
Clinical Trials Non-small-cell lung carcinoma
Colorectal Adenocarcinoma Vandetanib
FDA RET proto-oncogene
Incidence Lung cancer
Inhibitor Protein kinase inhibitor
Lung Organic compounds
Lung Cancer Piperidines
Melanoma Chemical compounds
Multiple Endocrine Neoplasia Tyrosine kinase receptors
Mutation NSCLC
Neuroblastoma RET mutations tumor
Neuroendocrine Tumors Tumors
Oncogene Organ systems
Organ Invasive breast cancers
Papillary Thyroid Carcinoma
Pathogenesis
Receptors
RET
Small Intestine
Somatic
Sorafenib
Sunitinib
Tumor
Tyrosine Kinase
Tyrosine Kinase Inhibitors

Semantics

Type Source Name
disease MESH development
drug DRUGBANK Nintedanib
drug DRUGBANK Alectinib
drug DRUGBANK Lenvatinib
drug DRUGBANK Ponatinib
drug DRUGBANK Regorafenib
drug DRUGBANK Cabozantinib
drug DRUGBANK Vandetanib
drug DRUGBANK Sorafenib
drug DRUGBANK Sunitinib
drug DRUGBANK L-Tyrosine
disease MESH neuroendocrine tumors
disease MESH neuroblastoma
pathway KEGG Small cell lung cancer
disease MESH small cell lung cancer
pathway KEGG Melanoma
disease MESH melanoma
disease MESH adenocarcinomas
pathway KEGG Non-small cell lung cancer
disease MESH non-small cell lung cancer
disease MESH papillary thyroid carcinoma
disease MESH multiple endocrine neoplasia
disease MESH tumors

Original Article

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