Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The current treatment standards include complete surgical resection for localized resectable disease and systemic therapy with mitotane alone or in combination with etoposide, doxorubicin, and cisplatin in patients with advanced ACC. However, the efficacy of systemic therapy in ACC is very limited, with high rates of toxicities. The understanding of altered molecular pathways is critically important to identify effective treatment options that currently do not exist. In this review, we discuss the results of recent advanced in molecular profiling of ACC with the focus on dysregulated pathways from various genomic and epigenetic dysregulation. We discuss the potential translational therapeutic implication of molecular alterations. In addition, we review and summarize the results of recent clinical trials and ongoing trials.

: Improved understanding of the genomic and molecular landscape of acute myeloid leukemia (AML) has resulted in significant evolution of our understanding of AML biology and allows refined prognostication for those receiving standard combination chemotherapy induction. This dramatic increase in knowledge preceded, and was somewhat responsible for, at least some of eight new FDA drug approvals for AML. This review discusses the impact of genomics on clinical care of AML patients and highlights newly approved FDA drugs. Despite these recent clinical advances, however, the outcome for most patients diagnosed with AML remains dire. Thus, we describe here some of the challenges identified with treating AML including off-target toxicity, drug transporters, clonal heterogeneity, and adaptive resistance, and some of the most promising opportunities for improved therapy.