Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options

Area of Science:

• Oncology
• Genomics
• Pharmacology

Background:

• Adrenocortical carcinoma (ACC) is a rare cancer with limited treatment options.
• In silico analysis offers a strategy to identify potential therapies by matching drugs to genomic alterations.
• Genomic profiling is crucial for understanding tumor heterogeneity and guiding treatment in rare cancers.

Purpose of the Study:

• To identify FDA-approved and investigational drugs targeting genomic alterations found in adrenocortical carcinoma (ACC).
• To assess the proportion of ACC patients whose tumors harbor potentially targetable genetic alterations.
• To highlight emerging therapeutic strategies for ACC based on in silico drug screening.

Main Methods:

• Screened FDA-approved and clinical trial drugs against genomic alterations in adrenocortical carcinoma (ACC) patients.
• Utilized databases like My Cancer Genome and the National Cancer Institute for drug and genetic alteration data.
• Linked 155 FDA-approved drugs and 905 clinical trial drugs to 375 genes from 89 TCGA patients.

Main Results:

• Identified frequently altered genes in ACC: TP53 (20%), BRD9 (13%), TERT (13%), CTNNB1 (13%), CDK4 (7%), FLT4 (7%), and MDM2 (7%).
• TP53-modulating drugs showed potential efficacy in 20-26% of patients; Wnt signaling inhibitors in 15%.
• 67% of ACC patients had genomic alterations potentially targetable by existing or investigational drugs.

Conclusions:

• A significant proportion of adrenocortical carcinoma (ACC) patients possess targetable genomic alterations.
• This study identifies promising therapeutic avenues, including TP53-targeting and Wnt pathway drugs, for ACC.
• Emerging drug options identified in this analysis warrant further investigation in clinical trials for adrenocortical carcinoma.