ABSTRACT
As a result of intense genetic studies of families with specific mutations, the road to better therapeutic intervention for pheochromocytoma (PHEOs) and parangangliomas (PGLs) has more recently become populated with several promising molecular targets. Consequently a change in paradigm from a previous view on nonspecific therapy has shifted towards more selective molecular targeted therapies. In particular, malignant PHEOs/PGLs, more specifically the tumors that result from mutations in succinate dehydrogenase subunit B (SDHB), are a clear concern, and novel therapies should be developed to address this problem. Here we summarize current and future therapeutic approaches.
Subject(s)
Adrenal Gland Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Paraganglioma/drug therapy , Pheochromocytoma/drug therapy , Succinate Dehydrogenase/genetics , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/metabolism , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Humans , Molecular Targeted Therapy , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Paraganglioma/genetics , Paraganglioma/metabolism , Paraganglioma/secondary , Pheochromocytoma/genetics , Pheochromocytoma/metabolism , Pheochromocytoma/secondary , Succinate Dehydrogenase/metabolismABSTRACT
Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and will be discussed along with advances in its treatment.