title: Current and emerging therapies for advanced adrenocortical carcinoma.
abstract: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with a poor prognosis. Complete surgical resection offers the only potential for cure; however, even after apparently successful excision, local or metastatic recurrence is frequent. Treatment options for advanced ACC are severely limited. Mitotane is the only recognized adrenolytic therapy available; however, response rates are modest and unpredictable whereas systemic toxicities are significant. Reported responses to conventional cytotoxic chemotherapy have also been disappointing, and the rarity of ACC had hampered the ability to undertake randomized clinical studies until the establishment of the First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma. This yet-to-be reported study seeks to identify the most effective first- and second-line cytotoxic regimens. The past decade has also seen increasing research into the molecular pathogenesis of ACCs, with particular interest in the insulin-like growth factor signaling pathway. The widespread development of small molecule tyrosine kinase inhibitors in broader oncological practice is now allowing for the rational selection of targeted therapies to study in ACC. In this review, we discuss the currently available therapeutic options for patients with advanced ACC and detail the molecular rationale behind, and clinical evidence for, novel and emerging therapies.
authors.affiliation: Cancer Genetics Unit, Hormones and Cancer Group, Kolling Institute of Medical Research, Department of Endocrinology, Royal North Shore Hospital, St. Leonards 2065 NSW Australia. lyndal.tacon@sydney.edu.au
authors.forename: Lyndal J
authors.initials: LJ
authors.lastname: Tacon
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Prichard
authors.forename: Patsy S H
authors.initials: PS
authors.lastname: Soon
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Clifton-Bligh
authors.forename: Stan B
authors.initials: SB
authors.lastname: Sidhu
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000628:therapy*; D018268:Adrenocortical Carcinoma / Q000628:therapy*; D000818:Animals; D006801:Humans