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Signaling Pathways in Adrenocortical Cancer
Author(s) -
KIRSCHNER LAWRENCE S.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04338.x
Subject(s) - signal transduction , adrenocortical carcinoma , cancer research , protein kinase b , biology , cancer , kinase , protein kinase a , carcinogenesis , medicine , endocrinology , microbiology and biotechnology
A bstract : Adrenocortical carcinoma is a rare tumor that carries a very poor prognosis. Despite efforts to develop new therapeutic regimens to treat this disease, surgery remains the mainstay of treatment. Laboratory studies of adrenocortical cancers have revealed a wide variety of signaling pathways that can be altered in these neoplasms. Although ACTH signaling through adenylyl cyclase and protein kinase A is important for normal adrenal cellular physiology, there is evidence to suggest that this pathway may inhibit the growth of adrenocortical tumors, and that inactivation of the ACTH receptor may promote tumor formation. Although multiple signal transduction pathways are essential for normal adrenal growth and hormone secretion, efforts to identify events required for neoplastic transformation have met with limited success. Alterations that have frequently been observed in adrenocortical carcinoma include up‐regulation of the IGF‐II system, as well as mutations in TP53 and RAS . Current studies aim to elucidate the mechanisms of tumor growth by studying proproliferative signaling pathways, such as those involving Akt/PKB and the mitogen‐activated protein kinases (MAPKs). Although studies of single pathways have been helpful in guiding investigations, new tools to study the integration and multiplicity of signaling pathways hold the hope of improved understanding of the signaling pathway alterations in adrenocortical cancer.