Article

Metastatic pheochromocytoma and paraganglioma: focus on therapeutics.

Paris-Descartes University, INSERM U-970, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hypertension Unit, Paris cedex 15, France.
Hormone and Metabolic Research (impact factor: 2.19). 02/2012; 44(5):390-9. DOI:10.1055/s-0031-1299707
Source: PubMed

ABSTRACT Metastatic pheochromocytomas and paragangliomas are rare and challenging tumors. The tumor burden, combined with excessive catecholamine production, predispose to a broad spectrum of complications that range from spinal cord compression to any organ damage, all of which may lead to decreased quality of life and overall survival. Current therapies include surgery, systemic chemotherapy and radiopharmaceutical agents. Surgery is often a preferred therapy because it may cure or allow a long-term remission in patients with locoregional or isolated resectable distant metastases. Additionally, surgery can palliate symptoms related to tumor burden or catecholamine excess. However, in patients for whom surgery is not an option, systemic chemotherapy and radiopharmaceutical agents are preferred options. Systemic chemotherapy and radiopharmaceutical agents such as 131I-Metaiodobenzylguanidine (131I-MIBG) may cause partial responses or stabilization of disease with better blood pressure control and symptomatic and performance status improvement. However, as these therapies are only palliative, patients' quality of life and personal preferences should always be considered. The recognition of molecular pathways involved in the pheochromocytoma and paraganglioma tumorigenesis has driven the development of new therapeutic options. Agents such as tyrosine kinase, MAPK, PI3K, or hypoxia inducible factor inhibitors, alone or in combination, may represent novel therapeutic strategies that could be evaluated in prospective clinical trials. Transcriptional profiling and the development of personalized cancer medicine will help to pave the way for more specific therapeutic approaches and combinations.

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  • Article: High-throughput screening for growth inhibitors using a yeast model of familial paraganglioma.
    Irina Bancos, John Paul Bida, Defeng Tian, Mary Bundrick, Kristen John, Molly Nelson Holte, Yeng F Her, Debra Evans, Dyana T Saenz, Eric M Poeschla, Derek Hook, Gunda Georg, L James Maher
    [show abstract] [hide abstract]
    ABSTRACT: Classical tumor suppressor genes block neoplasia by regulating cell growth and death. A remarkable puzzle is therefore presented by familial paraganglioma (PGL), a neuroendocrine cancer where the tumor suppressor genes encode subunits of succinate dehydrogenase (SDH), an enzyme of the tricarboxylic acid (TCA) cycle of central metabolism. Loss of SDH initiates PGL through mechanisms that remain unclear. Could this metabolic defect provide a novel opportunity for chemotherapy of PGL? We report the results of high throughput screening to identify compounds differentially toxic to SDH mutant cells using a powerful (yeast) model of PGL. Screening more than 200,000 compounds identifies 12 compounds that are differentially toxic to SDH-mutant yeast. Interestingly, two of the agents, dequalinium and tetraethylthiuram disulfide (disulfiram), are anti-malarials with the latter reported to be a glycolysis inhibitor. We show that four of the additional hits are potent inhibitors of yeast alcohol dehydrogenase. Because alcohol dehydrogenase regenerates NAD in glycolytic cells that lack TCA cycle function, this result raises the possibility that lactate dehydrogenase, which plays the equivalent role in human cells, might be a target of interest for PGL therapy. We confirm that human cells deficient in SDH are differentially sensitive to a lactate dehydrogenase inhibitor.
    PLoS ONE 01/2013; 8(2):e56827. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

blood pressure control
 
cancer medicine
 
catecholamine excess
 
Current therapies
 
excessive catecholamine production
 
hypoxia inducible factor inhibitors
 
long-term remission
 
molecular pathways
 
new therapeutic options
 
novel therapeutic strategies
 
paraganglioma tumorigenesis
 
performance status improvement
 
personal preferences
 
preferred therapy
 
prospective clinical trials
 
radiopharmaceutical agents
 
specific therapeutic approaches
 
systemic chemotherapy
 
Transcriptional profiling
 
tumor burden