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Adrenocortical carcinoma - towards genomics guided clinical care
Joakim Crona1, Felix Beuschlein2,3
1Department of Medical Sciences, Uppsala Universitet, Uppsala, Sweden. Joakim.crona@medsci.uu.se.
Abstract:
Adrenocortical carcinoma (ACC) is an aggressive and rare neoplasm that originates in the cortex of the adrenal gland. The disease is associated with heterogeneous but mostly poor outcomes and lacks effective pharmaceutical treatment options. Multi-omics studies have defined the landscape of molecular alterations in ACC. Specific molecular signatures can be detected in body fluids, potentially enabling improved diagnostic applications for patients with adrenal tumours. Importantly, pan-molecular data sets further reveal a spectrum within ACC, with three major subgroups that have different disease outcomes. These new subgroups have value as prognostic biomarkers. Research has revealed that the p53-RB and the WNT-β-catenin pathways are common disease drivers in ACC. However, these pathways remain difficult to target by therapeutic interventions. Instead, a unique characteristic of ACC is steroidogenic differentiation, which has emerged as a potential treatment target, with several agents undergoing preclinical or clinical investigations. Finally, a large proportion of ACC tumours have genetic profiles that are associated with promising therapeutic responsiveness in other cancers. All these opportunities now await translation from the laboratory into the clinical setting, thereby offering a real potential of improved survival outcomes and increased quality of life for patients with this serious condition.
Insights
Adrenocortical carcinoma (ACC) is a rare cancer with poor outcomes. New molecular subgroups and steroidogenic differentiation offer potential as prognostic biomarkers and therapeutic targets for improved patient survival.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Adrenocortical carcinoma (ACC) is an aggressive rare cancer with poor prognosis and limited pharmaceutical options.
- Multi-omics studies have elucidated molecular alterations in ACC, revealing distinct subgroups and potential diagnostic biomarkers in body fluids.
Purpose of the Study:
- To summarize the current understanding of adrenocortical carcinoma molecular landscape.
- To highlight emerging therapeutic targets and prognostic biomarkers for ACC.
- To discuss the translation of research findings into clinical applications.
Main Methods:
- Review of multi-omics studies in adrenocortical carcinoma.
- Analysis of molecular signatures for diagnostic and prognostic potential.
- Investigation of common disease drivers (p53-RB, WNT-β-catenin) and potential therapeutic targets (steroidogenic differentiation).
Main Results:
- ACC exhibits molecular heterogeneity with three major subgroups linked to different outcomes, serving as prognostic biomarkers.
- The p53-RB and WNT-β-catenin pathways are identified as key drivers but are challenging to target therapeutically.
- Steroidogenic differentiation presents a promising therapeutic avenue, with agents under investigation.
Conclusions:
- Molecular profiling of ACC reveals distinct subgroups and potential biomarkers for improved diagnostics and prognostics.
- Targeting steroidogenic differentiation and leveraging genetic profiles associated with therapeutic responsiveness hold promise for ACC treatment.
- Translational research is crucial to convert laboratory findings into improved clinical outcomes and quality of life for ACC patients.
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