Therapies targeting the signal pathways of pheochromocytoma and paraganglioma

Pheochromocytoma and paraganglioma (PCC/PGL) are rare tumors that originate from adrenal or extra-adrenal chromaffin cells. A significant clinical manifestation of PCC/PGL is that the tumors release a large number of catecholamines continuously or intermittently, causing persistent or paroxysmal hypertension and multiple organ functions and metabolic disorders. Though majority of the tumors are non-metastatic, about 10% are metastatic tumors. Others even have estimated that the rate of metastasis may be as high as 26%. The disease is most common in individuals ranging from 20 to 50 years old and the age of onset strongly depends on the genetic background: patients with germline mutations in susceptible genes have an earlier presentation. Besides, there are no significant differences in the incidence between men and women. At present, traditional treatments, such as surgical treatment, radionuclide therapy, and chemotherapy are still prior choices. However, they all have several deficiencies so that the effects are not extremely significant. Contemporary studies have shown that hypoxia-associated signal pathway, associated with the cluster 1 genes of PCC/PGL, and increased kinase signal pathways, associated with the cluster 2 genes of PCC/PGL, are the two major pathways involving the molecular pathogenesis of PCC/PGL, indicating that PCC/PGL can be treated with targeted therapies in emerging trends. This article reviews the progress of molecular-targeted therapies for PCC/PGL.