Next-generation therapies for adrenocortical carcinoma

Area of Science:

• Oncology
• Pharmacology

Background:

• Metastatic adrenocortical carcinoma (ACC) treatment relies on etoposide, doxorubicin, cisplatin, and mitotane (EDP-M).
• Despite treatment, advanced ACC prognosis remains poor, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To review current systemic treatments for ACC.
• To provide a comprehensive overview of novel therapeutic approaches investigated for ACC.
• To discuss reasons for trial failures and identify potential new drug targets.

Main Methods:

• Literature review of systemic therapies for ACC.
• Analysis of clinical trial outcomes for novel ACC treatments.
• Exploration of molecular studies to identify new therapeutic targets.

Main Results:

• Past novel therapeutic approaches, including IGF pathway inhibitors, TKIs, radionuclide therapy, and immunotherapy, have yielded disappointing results.
• Potential reasons for treatment failure include drug interactions with mitotane, disease heterogeneity, and resistance to immunotherapy.
• Molecular studies have identified potential new targets such as wnt/β-catenin, cyclin-dependent kinases, and PARP1.

Conclusions:

• Current systemic therapies for advanced ACC are insufficient.
• Novel treatment strategies for ACC have largely failed due to various factors.
• Emerging molecular targets offer promise for developing next-generation ACC therapies.