Drug Response Signatures in Rare Adrenocortical Carcinoma & Patient-Patient Similarity Networks

Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis and an overall 5-year mortality rate of 75-90%. ACC is challenging to diagnose early due to a lack of specific notable symptoms. Chemotherapy, radiotherapy, and the adrenolytic agent, mitotane, are the current standard treatments for unresectable or metastatic ACC, but all are palliative. Furthermore, to date, there is only one FDA-approved agent, mitotane, with limited efficacy and significant toxicity. Predictive markers of response that correlate with clinical endpoints remain elusive and warrant further investigation through the analysis of -omics profiling, which may aid in improving therapeutic efficiency.

We have begun a concerted effort to tackle the challenges presented by this cancer through the collection of several unpublished pharmacogenomics-related datasets in both preclinical models and patient samples with more expected as part of an ongoing clinical trial Tissue Procurement and Natural History Study of Neuroendocrine Neoplasms (NENs) Including Adrenocortical Carcinoma (NCT05237934) at the National Cancer Institute (NCI).

Our proposal is aimed at identifying drug response signatures in ACC preclinical models and translating these for use with patient data building on previous methodologies we have worked to develop (e.g., TumorComparer and CausalPath). We aim to integrate data and analytical results into our CellMiner Cross-Database (CellMinerCDB; https://discover.nci.nih.gov/rsconnect/cellminercdb/) web application to allow further exploration and use by clinicians.