{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:51:33Z","timestamp":1777395093793,"version":"3.51.4"},"reference-count":61,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rodrigo Toledo and Camilo Jimenez have received financial research support by a Paradifference Foundation Research Grant."},{"name":"Fundaci\u00f3n Olga Torres Emergent Researcher Grant"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Inactivating mutations of the succinate dehydrogenase subunit B (<ns4:italic>SDHB<\/ns4:italic>) gene and the subsequent stabilization and activation of the hypoxia-inducible factor 2-alpha (HIF2\u03b1) unit are recognized hallmarks associated with the development of metastatic pheochromocytomas and paragangliomas (MPPG). Despite this discovery, the development of systemic therapies for patients with MPPG has been very slow. The rarity of the disease, the lack of preclinical animal models, and the impracticable development of large clinical trials has hindered the therapeutic progress for MPPG. Chemotherapy and low-specific activity<ns4:sup>131<\/ns4:sup>meta-iodo-benzyl-guanidine (MIBG) (manufactured by simple isotope exchange methodology) led to positive clinical responses in about a third of patients. Molecular targeted therapies were introduced into oncological clinical practice at the beginning of the 21st century. These therapies have been demonstrated to be effective for patients with cancers that previously exhibited limited responses to systemic chemotherapy, such as kidney and thyroid carcinomas and pancreatic neuroendocrine tumors. The pathogenesis of MPPG overlaps in some way with the pathogenesis of kidney, medullary thyroid, and pancreatic neuroendocrine carcinomas, providing scientific support to explore molecular targeted therapies such as tyrosine kinase and HIF inhibitors.<\/ns4:p>","DOI":"10.12688\/f1000research.13995.1","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T08:40:05Z","timestamp":1532940005000},"page":"1148","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Recent advances in the management of malignant pheochromocytoma and paraganglioma: focus on tyrosine kinase and hypoxia-inducible factor 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