Work

Beyond mitotane: next-generation therapeutic landscapes in adrenocortical carcinoma

Year: 2026

Type: article

Abstract: The clinical management of adrenocortical carcinoma (ACC) has long been defined by its resistance to conventional therapies. Since the FIRM-ACT trial established the combination of etoposide, doxorubicin, and cisplatin plus mitotane (EDP-M) as the frontline standard, overall survival for metastatic patients has remained stubbornly low. This plateau in efficacy with cytotoxic regimes has necessitated a shift towards precision oncology and immunotherapy. However, translating the success of immune checkpoint inhibitors seen in other malignancies to ACC has proven exceptionally difficult. The primary challenge in the present therapeutic landscape of immunotherapy is the unique biology of the adrenal cortex, which creates an intrinsic immunologically privileged site. This review will address these current immunological hurdles but also explore novel strategies designed to bypass this barrier entirely. By shifting focus towards mechanisms that do not solely rely on the traditional engagement of adaptive immune system - such as the targeted delivery of cytotoxic payloads via antibody-drug conjugates (ADCs) or the androgen-mediated activation of myeloid cells to clear pro-tumoural populations - the field is moving towards a future where the 'cold' nature of the tumour microenvironment may no longer dictate the limits of therapeutic success.

Source: Endocrine Oncology

DOI: 10.1530/eo-26-0040

Authors: Keya Kotecha, Katia Mariniello, Leonardo Guasti

Institutions: Queen Mary University of London, William Harvey Research Institute

Language: English

Topic: Adrenal and Paraganglionic Tumors

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Barts Charity, Medical Research Council