Lysodren (mitotane)

Despite multiple adverse prognostic indicators, the patient has remained disease-free for over 5 years following adrenalectomy and adjuvant low-dose mitotane therapy. These findings suggest that GNAS activation may drive steroidogenesis while attenuating malignant progression, as demonstrated by integrated morphologic and genomic assessment in this case.

identifying agents capable of complementing or replacing standard therapy remains a central challenge in ACC research. Our findings suggest that celastrol is a potent bioactive compound with activity against both monolayer and 3D ACC models, offering potential translational relevance. By elucidating ER stress as a shared mechanism between celastrol and mitotane, our work supports further exploration of this pathway as a strategy to potentially improve therapeutic outcomes in ACC patients.

The patient was started on mitotane and metyrapone, followed by 8 cycles of etoposide-doxorubicin-cisplatin plus mitotane. The patient underwent complete surgical resection, achieving full remission. More than 1 year later, she remains disease free.

P=N/A, N=62, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P2, N=30, Active, not recruiting, National Cancer Center, Korea | Enrolling by invitation --> Active, not recruiting | Trial completion date: Aug 2026 --> Feb 2027 | Trial primary completion date: Aug 2025 --> Feb 2027

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.

Current therapy for advanced adrenocortical carcinoma (ACC) is represented by EDP-M (etoposide, doxorubicin, cisplatin + mitotane), but its efficacy is limited and new approaches are needed. Interestingly, Myt1 increase after AZD1775 treatment in primary ACC cells was reverted by EDP-M cotreatment. Overall, our data in in vitro and in vivo preclinical ACC models support AZD1775 as a promising ACC therapeutic option, and its combination with EDP-M as a useful strategy to enhance drug efficacy, reduce cortisol secretion, prevent drug resistance and minimize side effects by reducing the therapeutic dosage.

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.