MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death.

All other lines of therapy, including mitotane, were stopped before pembrolizumab initiation. No treatment-related deaths occurred. Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile.

Postoperatively, hypertension and potassium levels normalized with reduced antihypertensive therapy; she commenced steroid replacement and adjuvant mitotane. At early follow‑up, she remained clinically stable and disease‑free. This case highlights the importance of considering OACC in patients with large adrenal masses and resistant hypertension, demonstrates the value of multidisciplinary management and definitive surgery, and contributes to the limited evidence guiding adjuvant therapy for this uncommon tumor.

Surgery and mitotane-based chemotherapy remain the standard of care, and new treatment strategies are needed...However, non-specific uptake by monocytes and endothelial cells reduces delivery efficiency. These findings highlight the need for strategies to enhance tumour-specific targeting and improve biodistribution in future theranostic applications.

P=N/A, N=400, Active, not recruiting, University of Wuerzburg | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

Following surgery and adjuvant mitotane therapy, the patient showed no recurrence at a 5-year follow-up...This case was the first case report of myxoid ACC with a 1p deletion, which was reported to be detected in 67% of ACC and 9% of adenoma but not in hyperplasia, supporting the correlation of this aberration with tumorigenesis. In conclusion, 1p deletion may be relevant to tumorigenesis in myxoid ACC.

First-line mitotane therapy failed due to toxicity and progressive disease. We report a patient with metastatic adrenocortical carcinoma in Lynch syndrome who demonstrated an excellent response to pembrolizumab. Genetic analyses can play a beneficial role in cases of adrenocortical carcinoma.

Mitotane increases GDF-15 levels and is associated with poor response to ICI. GDF-15 may mediate reduced infiltration with immune cells in ACC.

P2, N=3, Terminated, M.D. Anderson Cancer Center | Completed --> Terminated; Slow accrual

P3, N=240, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2029 | Trial primary completion date: Jan 2025 --> Jan 2029

P2, N=28, Recruiting, West China Hospital | Trial completion date: Dec 2030 --> Dec 2031

Current treatment approaches, largely adapted from adult protocols, center on surgery and chemotherapy, including mitotane...By leveraging molecular insights and fostering global collaboration, the field can move toward personalized medicine, improving outcomes and quality of life for children with this challenging disease. Expanding clinical trials, refining diagnostic tools, and integrating novel therapies into treatment regimens will be critical in bridging the gap between pediatric and adult ACC treatment success.