Lysodren (mitotane)

This is the second report of ACC associated PJS in a rare germline variant of STK11. Although rare, loss of STK11 function may lead to cancers outside expected sites in PJS cases.

Follow-up 18F-FDG PET/CT confirmed a sustained partial response per response evaluation criteria in solid tumors (RECIST) 1.1, accompanied by significant metabolic improvement with regression of metastatic burden with evident central photopenia in peritoneal lesions. This case illustrates how multi-faceted genomic analysis can rationalize aggressive combination immunotherapy in refractory ACC.

SMAC-2 originated from a metastatic EDP-M-treated ACC in a female patient with hypercortisolism and hyperandrogenism, while SMAC-3 derived from a male patient with a mitotane-treated local recurrence, with no sign of hypercortisolism...Experiments were carried out to study the stability of the two cell lines. SMAC-2 and SMAC-3 display unique molecular and functional features, expanding the repertoire of experimental ACC models and representing valuable tools for preclinical research alongside established cell lines.

P=N/A, N=400, Active, not recruiting, University of Wuerzburg | Trial completion date: Dec 2027 --> Dec 2029 | Trial primary completion date: Dec 2025 --> Dec 2027

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.