Current and emerging therapies for advanced adrenocortical carcinoma

Area of Science:

• Oncology
• Endocrinology
• Cancer Research

Background:

• Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with a poor prognosis and high recurrence rates.
• Current treatment options for advanced ACC are limited, with modest efficacy and significant toxicities associated with existing therapies like mitotane and conventional chemotherapy.
• The rarity of ACC has historically hindered large-scale clinical research, but recent advancements are paving the way for novel therapeutic strategies.

Purpose of the Study:

• To review current therapeutic options for advanced adrenocortical carcinoma.
• To discuss the molecular pathogenesis of ACC, focusing on the insulin-like growth factor signaling pathway.
• To explore novel and emerging targeted therapies based on molecular insights and clinical trial data.

Main Methods:

• Review of existing literature on adrenocortical carcinoma treatment.
• Analysis of molecular pathogenesis research, particularly the insulin-like growth factor pathway.
• Discussion of ongoing and recently established clinical trials, including the First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma.

Main Results:

• Mitotane offers limited and unpredictable responses with significant toxicity.
• Conventional chemotherapy has shown disappointing results in ACC.
• Emerging research into molecular pathways like IGF signaling is guiding the development of targeted therapies.

Conclusions:

• Complete surgical resection remains the only potential cure for ACC, but recurrence is common.
• Novel therapeutic strategies, including targeted therapies informed by molecular pathogenesis, are crucial for improving outcomes in advanced ACC.
• Ongoing clinical trials are essential for identifying effective first- and second-line treatment regimens for this rare malignancy.