Breakthrough in Adrenocortical Carcinoma Treatment: New Target Identified

Researchers have made significant progress in understanding the treatment of adrenocortical carcinoma, a rare and aggressive form of cancer. A study published in Nature Communications has identified delta-like non-canonical Notch ligand 1 (DLK1) as a cell surface protein with high expression in multiple refractory adult metastatic cancers, including small cell lung cancer and adrenocortical carcinoma. This breakthrough has led to the development of a new treatment targeting DLK1, which has shown promising results in vitro and in vivo models.

Key Takeaways:

• The study identified DLK1 as a cell surface protein with high expression in multiple refractory adult metastatic cancers, including adrenocortical carcinoma and small cell lung cancer.
• The research found that DLK1 regulates tumor cell plasticity and chemoresistance in adrenocortical carcinoma and supports an active phase I clinical trial targeting DLK1 with an antibody-drug conjugate in adrenocortical carcinoma and neuroendocrine neoplasms.
• The study revealed that genetic deletion of DLK1 in adrenocortical carcinoma dramatically downregulates the drug efflux protein ABCB1 and increases ADC payload and chemotherapy sensitivity through NOTCH1-mediated transdifferentiation.
• The research was funded by the U.S. Department of Health & Human Services | NIH | National Cancer Institute and ADC Therapeutics.
• The study was conducted by a team of researchers led by Nitin Roper from the National Cancer Institute (NCI), with additional authors including Nai-Yun Sun, Suresh Kumar, Yoo Sun Kim, and others.

Statistics:

• 16% of adrenocortical carcinoma patients have high expression of DLK1, which is associated with poor prognosis.
• 80% of patients with adrenocortical carcinoma have refractory disease, which is resistant to current treatments.
• The study found that DLK1 targeting antibody-drug conjugate (ADC) shows in vitro and in vivo activity in adrenocortical carcinoma models.
• The study concluded that DLK1 is an immunotherapeutic target that regulates tumor cell plasticity and chemoresistance in adrenocortical carcinoma.

Sources:

• NewsRx. Study Findings from National Cancer Institute (NCI) Broaden Understanding of Adrenocortical Carcinoma (Identification of the Notch Ligand Dlk1 As an Immunotherapeutic Target and Regulator of Tumor Cell Plasticity and Chemoresistance In ...). Health & Medicine Week. August 8, 2025; p 5383.
• National Cancer Institute (NCI). "Identification of the Notch Ligand Dlk1 As an Immunotherapeutic Target and Regulator of Tumor Cell Plasticity and Chemoresistance In Adrenocortical Carcinoma." Nature Communications, 2025;16(1).