Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. The majority of ACC patients have metastasis at the time of diagnosis, resulting in a 5-year survival rate of less than 35%. Complete surgical resection remains the standard of care today. Other commonly used pharmacological interventions include the adrenotoxic drug mitotane (o,p′-DDD), which is administered either alone or in combination with other cytotoxic chemotherapy, such as etoposide, doxorubicin, and platinum agents. Because this method of treatment has a relatively low response rate and carries significant systemic toxicity, better treatment methods are critically needed for more effective targeting and inhibition of ACC. An ACC cell line (H295R) from a patient presenting with elevated plasma steroid hormones shows a high level of SR-B1 expression and takes up HDL mimetic cargo both in vitro and in vivo. SR-B1 (SCARB1) is a scavenger receptor typically found on cell surface of adrenal, liver and gonadal tissues.
Our platform selectively delivers drug payloads to cells that express SR-B1, making ACC a good first target. In addition, elevated SR-B1 expression has been reported or is suspected in numerous cancer types, including: bile duct cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gastrointestinal cancer, liver cancer, nasopharyngeal cancer, ovarian cancer, pancreatic cancer, prostate cancer, adrenocortical carcinoma, lung adenocarcinoma, renal cell carcinoma, leukemia, lymphoma, neuroblastoma, and sarcoma. We plan to systematically investigate these tumors through in vivo and in vitro studies to determine which of these tumor types might also be amenable to an SR-B1 targeted approach.
For ACC and subsquent cancer indications, we beleive our solution will provide benefit to patients by concentrating drug payloads to cells expressing the SR-B1 receptor while avoiding sensitive tissues in the heart, brain and other organs.