A large international study led by researchers at Queen Mary University of London has identified a new biomarker that could support the diagnosis and treatment of adrenal cancer.
3d rendered medically accurate illustration of the adrenal gland. Photo credit: Sebastian Kaulitzki
Adrenocortical carcinoma (ACC) is a rare but aggressive cancer that develops in the outer layer of the adrenal gland—small organs located on top of the kidneys that produce essential hormones. Unfortunately, ACC is often diagnosed late, after the cancer has already spread, leading to a poor prognosis. For patients with advanced ACC, the five-year survival rate is less than 15%.
The study, published in Cancer Communications, was led by Dr Katia Mariniello and Dr James Pittaway in the laboratory of Professor Leonardo Guasti at the Centre for Endocrinology, William Harvey Research Institute. The researchers discovered that a protein called DLK1 (delta-like non-canonical Notch ligand 1) plays a key role in ACC. They found that ACC tumours have high levels of DLK1, and patients with increased DLK1 levels face a higher risk of cancer recurrence.
Crucially, DLK1 can also be detected in the blood of patients, providing a highly reliable way to determine if adrenal tumours are cancerous. This can be done with a simple laboratory test (ELISA), offering for the first time in ACC new hope of a biomarker that could be widely used in clinical practice.
The study also explored the biological role of DLK1. In the growing embryo, DLK1 is active, developing the steroid producing cells in the adrenal gland, but in adults, it is normally inactive. However, in ACC patients, DLK1 becomes active again, contributing to the production of steroids and potentially driving cancer progression.
Dr Katia Mariniello, Postdoctoral Researcher at Queen Mary University of London and co-first author, said: “Given that DLK1 is expressed in very few healthy tissues in humans after birth, is highly expressed in ACC and shown to contribute to worse prognoses, it is a very attractive target for generating novel therapeutics and drug strategies.”
Dr James Pittaway, NIHR Academic Clinical Lecturer at Queen Mary University of London and co-first author, said: “This study reveals an important role for DLK1 in ACC both as a novel biomarker but also as a preferential target for drug therapies. As DLK1 is expressed in other common malignancies, these findings are widely applicable both in enhancing the understanding of its role in these settings and informing novel monitoring and therapeutic strategies”.