Targeting Pituitary Tumors

Abstract

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 dopamine₂ 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 α-adrenoceptor blocker that appears to inhibit nuclear signaling mediated by nuclear factor kappa-B (NFĸB), 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.

The Immunophilin-Like Protein XAP2 Is a Negative Regulator of Estrogen Signaling through Interaction with Estrogen Receptor α

“…Several studies have demonstrated that the tumorigenic effects of estrogens are primarily mediated by ERα. Lifetime exposure and high estrogen levels and thus high ER transcriptional activity represent a risk factor for developing tumors in breast [21] , endometrial [22] , ovarian [23] pituitary [24] and thyroid tissues [25] . In contrast, ERβ has been shown to possess a tumor suppressive effect in tissues such as the prostate [26] and colon [27] .…”

Physiopathology of somatolactotroph cells: from transduction mechanisms to cotargeting therapy

“…Interestingly, pharmacological or molecular inhibition of Akt similarly reduces GH3 viability and NF‐κB binding, suggesting that the constitutive activation of NF‐κB observed in pituitary tumor cells may be, at least in part, mediated by Akt 74 . Thus, doxasozin, an alpha‐adrenoreceptor blocker that appears to inhibit nuclear signaling mediated by NF‐κB, may represent new medical therapy for some problematic pituitary tumors 75,76 …”

“…74 Thus, doxasozin, an alphaadrenoreceptor blocker that appears to inhibit nuclear signaling mediated by NF-B, may represent new medical therapy for some problematic pituitary tumors. 75,76 Another target of the PI3K/Akt pathway is mTOR. Previous studies have shown that rapamycin derivative RAD001 (everolimus) induces antiproliferative effects in GH-secreting pituitary tumor cells in vitro, by regulating cell cycle arrest.…”