Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Adrenal cortex tumors (ACTs) encompass benign adrenocortical adenomas (ACAs) and aggressive adrenocortical carcinomas (ACCs).
• Functional ACAs can cause Cushing's or Conn's syndrome; ACCs are rare but aggressive, potentially causing hypersecretion.
• Genetic studies implicate PKA, Wnt/β-catenin, and P53 pathways in ACT development.

Purpose of the Study:

• To review existing mouse models of ACTs, focusing on PKA and Wnt/β-catenin pathways.
• To evaluate the advantages and limitations of current xenografted and genetically engineered models.
• To identify improvements needed for next-generation mouse models of adrenal diseases.

Main Methods:

• Review of existing literature on xenografted and genetically engineered mouse models of ACTs.
• Focus on models investigating the roles of protein kinase A (PKA) and Wnt/β-catenin signaling pathways.
• Analysis of model utility for studying tumor development and endocrine disorders.

Main Results:

• Various mouse models exist, including xenograft and genetically engineered types, to study ACTs.
• These models have been instrumental in exploring the functional significance of candidate genes in PKA and Wnt/β-catenin pathways.
• Current models offer insights but possess limitations that hinder comprehensive mechanistic and therapeutic studies.

Conclusions:

• Mouse models are essential for dissecting ACT pathogenesis and endocrine dysfunctions.
• Existing models provide valuable tools but require further refinement for improved therapeutic screening and mechanistic insights.
• Future development should focus on enhancing the predictive power and translational relevance of ACT mouse models.