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Targeted therapies for adrenocortical carcinoma: IGF and beyond
Michael J Demeure1, Kimberly J Bussey, Lawrence S Kirschner
1Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Abstract:
Standard chemotherapy for adrenocortical cancer currently is under evaluation in the context of the recently completed FIRM-ACT evaluating the combination of mitotane with either streptozocin or etoposide, cisplatin, and doxorubicin. New agents are eagerly sought by the ACC community that hopes to make progress against this deadly disease. Investigators have begun to dissect the molecular and genomic context of ACC with a goal of identifying potential novel therapeutic agents. One gene consistently overexpressed in ACC is insulin growth factor type 2. Targeting its receptor IGF1R has shown encouraging results in ACC cell lines and against murine xenografts. As a result, clinical trials to evaluate agents targeting the IGF1R have been done including mitotane and IMC-A12 (a monoclonal antibody) and the GALACCTIC trial that has just completed accrual to evaluate OSI-906, a small molecule IGF1R antagonist. On the horizon are other agents targeting other tyrosine kinases, including EGF and FGF, and novel strategies such as individualized tumor analysis to select treatment.
Insights
New treatments for adrenocortical cancer (ACC) are needed. Targeting the insulin growth factor type 2 receptor (IGF1R) shows promise, with ongoing clinical trials evaluating novel agents against this deadly cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Adrenocortical cancer (ACC) has limited standard treatment options.
- There is an urgent need for novel therapeutic agents to improve outcomes for ACC patients.
- Molecular and genomic studies are identifying potential therapeutic targets in ACC.
Purpose of the Study:
- To review current and emerging therapeutic strategies for adrenocortical cancer.
- To highlight the role of insulin-like growth factor 1 receptor (IGF1R) as a therapeutic target in ACC.
- To discuss ongoing and future clinical trials for novel ACC treatments.
Main Methods:
- Review of recent clinical trials and preclinical data for adrenocortical cancer treatments.
- Focus on agents targeting the insulin growth factor type 2 receptor (IGF1R).
- Discussion of emerging therapeutic strategies including tyrosine kinase inhibitors and personalized medicine.
Main Results:
- Standard chemotherapy regimens are under evaluation.
- Targeting IGF1R has shown encouraging results in preclinical models and early clinical studies.
- Clinical trials evaluating IGF1R inhibitors (e.g., OSI-906) have been conducted.
Conclusions:
- Targeting IGF1R represents a promising therapeutic strategy for adrenocortical cancer.
- Further investigation into IGF1R antagonists and other tyrosine kinase inhibitors is warranted.
- Personalized treatment approaches based on tumor analysis are on the horizon for ACC.
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