Targeting pituitary tumors.
BACKGROUND
Pituitary tumors are common and usually grow insidiously over many years. Rarely fatal, treatment still requires multiple cytoreductive surgeries and/or radiation therapy with its attendant side effects. As a disease process of regulatory pathways, pituitary tumors offer numerous potential therapeutic targets, and many, such as the membranal dopamine(2) and somatostatin receptors, have been successfully exploited for many years. Nuclear receptors, such as the estrogen receptor, peroxisome proliferator-activating receptor and retinoic acid receptor, are abundantly expressed in pituitary tumors, and a variety of increasingly potent and specific ligands are emerging. Subcellular therapies aimed at the pituitary tumor transforming gene may also have some utility in pituitary tumor management, though obstacles to targeting nuclear proteins using gene therapy still exist. Other novel agents such as doxazosin, an alpha-adrenoceptor blocker that appears to inhibit nuclear signaling mediated by nuclear factor kappa-B (NFkappaB), and epidermal growth factor receptor may also represent new and safe medical therapies for these benign but problematic tumors.


CONCLUSIONS
Increased understanding regarding the etiopathogenesis of pituitary tumors has identified new proteins and pathways that may lead to novel therapies. Empiric exploration of novel targeted therapies developed for other tumor types, guided by pharmacogenomic profiling studies, will likely reveal the utility of many of these novel targeted agents in the treatment of pituitary tumors.
Heaney
Anthony P
AP
Division of Endocrinology and Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, Calif., USA. aheaney@mednet.ucla.edu
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000818:Animals; D017292:Doxazosin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D008024:Ligands; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011799:Quinazolines / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D064249:Securin
D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D009363:Neoplasm Proteins; D047495:PPAR gamma; D011799:Quinazolines; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D064249:Securin; D017292:Doxazosin