Background Endocrine malignancies (including thyroid, adrenal, parathyroid, and pancreatic neuroendocrine tumors) are among the fastest growing cancer diagnoses in the United States, but it is difficult to distinguish benign from malignant tumors by routine clinical, laboratory, and imaging studies. So, even patients who have seemingly benign endocrine tumors often choose to undergo surgery to get a definitive diagnosis in the hopes of ruling out cancer. Most patients with endocrine cancers have a relatively good prognosis. However, anywhere from 10% to 40% (depending on tumor type) have aggressive disease which often cannot be reliably determined at the time of initial treatment. Prognostic markers which can reliably risk stratify patients with high risk of recurrence and death would help determine which patients should receive aggressive initial treatment and close follow up. Furthermore, prognostic markers may also help identify which patients are likely to respond to standard therapy and which patients do not respond to standard therapy if a distinct molecular phenotype is identified. Summary We are making progress with our pan-genomic (mRNA and microRNA expression, copy number changes, and DNA-methylation) analysis of endocrine neoplasms to identify candidate diagnostic and prognostic markers for endocrine malignancies (thyroid, adrenal, neuroendocrine pancreas), and to understand the dysregulated genes/pathways in endocrine cancers. From these analyses, we have identified a miR-30a-LOX axis important in thyroid cancer progression. Moreover, we have discovered that high LOX expression is significantly associated with higher mortality rates in patients with thyroid cancer and more aggressive tumors. We are currently defining if LOX (a secreted protein) can be targeted for cancer therapy and if it has intracellular function. In our integrated genomic analysis of adrenocortical carcinoma samples, we have identified a number of novel pathways that might be involved in adrenocortical carcinogenesis, including the Oncostatin M signaling pathway. Our studies demonstrate that this pathway is involved in caspase 3-dependent apoptosis and is targetable pathway for adrenocortical carcinoma therapy.
Showing the most recent 10 out of 57 publications
