From the Duke Cancer Institute archives. Content may be out of date.
Suzanne Wardell
Research that originated in a Duke Cancer Institute (DCI) laboratory contributed to Food and Drug Administration (FDA) approval of the first new endocrine therapy for breast cancer since 2002, and the only drug designed to target mutations in estrogen receptor 1 (ESR1).
Donald McDonnell, PhD, associate director For translational research at DCI and the Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology, directed the research team that led to the development of elacestrant (Orserdu, Stemline Therapeutics, Inc).
The new therapy, a selective estrogen receptor down-regulator (SERD), is indicated for the treatment of postmenopausal women or adult men with estrogen-receptor-positive/HER2-negative ESR1-mutated advanced or metastatic breast cancer who have been treated unsuccessfully with at least one previous endocrine therapy.
The FDA approved the therapy in January 2023.
Meeting a Need
Erik Nelson
The drug is the only SERD that can be taken orally, which makes it more convenient for patients. McDonnell said it fills a significant unmet need because up to 40% of patients diagnosed with ER-positive/HER2-negative breast cancer will acquire ESR1 mutations as the cancer advances. In most cases, these mutations will trigger resistance to standard endocrine therapies.
During the past decade, the McDonnell Lab has been focused on identifying and developing new endocrine therapies to treat advanced ER-positive breast cancer. This initiative has included revisiting older hormone therapies originally developed to treat osteoporosis or menopause symptoms.
Elacestrant, for example, was developed initially to treat hot flashes in post-menopausal women but was never approved for that use. Clinical trials demonstrated that RAD1901, as the therapy was known, stopped hot flashes at low doses but increased them at higher doses. McDonnell and researchers in his lab were intrigued by the pharmacology. “It turns out that the reason for RAD1901’s failure as a treatment for hot flashes was a useful property for a breast cancer drug,” McDonnell said.
Investigators who were trainees in the McDonnell Lab at the time, Suzanne E. Wardell, PhD, and Erik Nelson, PhD, determined that RAD1901 was effective at blocking the estrogen driving cancer cell growth by binding to its receptor, like a selective estrogen receptor modulator(SERM), and degrading the estrogen receptor, like a SERD.
Wardell and Nelson went on to demonstrate that RAD1901 inhibited tumor growth in mouse models. This was the springboard for continued investigations worldwide; culminating in the successful multicenter phase 3 clinical trial (EMERALD 2018–2022) that led to FDA approval. Wardell is now an assistant professor of pharmacology and cancer biology at Duke, in McDonnell’s lab. Nelson is now a professor of molecular and integrative physiology at the University of Illinois Urbana-Champaign.
“We’re already prescribing elacestrant for our patients,” said Heather Moore, CPP, PharmD, a clinical pharmacist with Duke Health, noting that the drug is currently being distributed nationally by two specialty pharmacies.
Researchers at the Duke Cancer Institute (DCI) are working with collaborators at leading academic medical centers to explore a faster, less invasive way to detect and analyze head and neck cancers using light and artificial intelligence.In a recent study published in Biophotonics Discovery, a DCI team led by Tuan Vo-Dinh, PhD, partnered with Maie St John, MD, and clinical researchers at the University of California, Los Angeles (UCLA), to demonstrate how a light-based imaging technique combined with machine learning could help distinguish cancerous tissue with high accuracy. The work is now continuing at Johns Hopkins University.Today, diagnosing many cancers such as thyroid and head and neck cancers often relies on pathology or fine needle aspiration (FNA). In an FNA procedure, a thin needle is inserted into a tumor to collect cells, which are then analyzed by a pathologist.“While these approaches are widely used, they can be time-consuming and don’t always give clear or definitive results,” Vo-Dinh said. “In some cases, patients may have to wait weeks for answers, and the accuracy can vary depending on sampling and interpretation.”The collaborative teams used a technology known as Dynamic Optical Contrast Imaging (DOCI), a technique developed at UCLA, which uses laser light to excite tissue. When exposed to this light, different molecules in the tissue emit fluorescence—subtle signals that vary depending on whether tissue is cancerous or healthy. The result is a color-coded “map” of the tissue that reflects its biological properties.“Instead of looking at one spot on the tissue sample, this technique provides spatial information across the entire tissue region monitored,” Vo-Dinh explained. “You can actually see differences in how cancerous and non-cancerous areas respond to light.”These light-based signals are incredibly rich—but also complex. That’s where machine learning comes in. Vo-Dinh’s team applied machine learning algorithms to analyze the complex imaging data generated by DOCI. The researchers trained AI models to recognize subtle patterns in the imaging data and distinguish between different types of thyroid cancer, specifically papillary and follicular thyroid cancers, and to determine whether tissue was cancerous.The results were promising. The machine learning system showed strong agreement with pathological findings, accurately identifying cancerous regions within the tissue samples.“This is an exciting proof of principle demonstration that combining photonics with AI can work together and provide meaningful, reliable answers,” Vo-Dinh said. “The performance we’re seeing so far is very encouraging.”While the research is still in its early stages, the potential implications for patient care are significant.Because this approach directly analyzes the tissue and does not rely on waiting for lab-based assays, it could eventually support faster, point-of-care cancer assessment. Imagine a future where clinicians may be able to use similar tools directly on tissue, potentially even during surgery, to guide decisions in real time.“It could reduce the need for repeat biopsies and long waiting periods,” Vo-Dinh said. “And because the technique is non-invasive, it may also make screening easier and more accessible for patients.”The work underscores the critical importance of collaboration across institutions and disciplines, bringing together clinical expertise, advanced imaging, and data science.“This is a very synergistic partnership,” Vo-Dinh said. “Each group contributes something essential, from clinical insight to optical technology to computational analysis. That kind of complementarity is what drives innovation.”Next steps will focus on expanding and refining the technology, with the goal of enabling real-time, in situ cancer detection.“We’re excited to continue this collaboration and explore how far this approach can go,” Vo-Dinh said.
Researchers at the Duke Cancer Institute (DCI) are working with collaborators at leading academic medical centers to explore a faster, less invasive way to detect and analyze head and neck cancers using light and artificial intelligence.In a recent study published in Biophotonics Discovery, a DCI team led by Tuan Vo-Dinh, PhD, partnered with Maie St John, MD, and clinical researchers at the University of California, Los Angeles (UCLA), to demonstrate how a light-based imaging technique combined with machine learning could help distinguish cancerous tissue with high accuracy. The work is now continuing at Johns Hopkins University.Today, diagnosing many cancers such as thyroid and head and neck cancers often relies on pathology or fine needle aspiration (FNA). In an FNA procedure, a thin needle is inserted into a tumor to collect cells, which are then analyzed by a pathologist.“While these approaches are widely used, they can be time-consuming and don’t always give clear or definitive results,” Vo-Dinh said. “In some cases, patients may have to wait weeks for answers, and the accuracy can vary depending on sampling and interpretation.”The collaborative teams used a technology known as Dynamic Optical Contrast Imaging (DOCI), a technique developed at UCLA, which uses laser light to excite tissue. When exposed to this light, different molecules in the tissue emit fluorescence—subtle signals that vary depending on whether tissue is cancerous or healthy. The result is a color-coded “map” of the tissue that reflects its biological properties.“Instead of looking at one spot on the tissue sample, this technique provides spatial information across the entire tissue region monitored,” Vo-Dinh explained. “You can actually see differences in how cancerous and non-cancerous areas respond to light.”These light-based signals are incredibly rich—but also complex. That’s where machine learning comes in. Vo-Dinh’s team applied machine learning algorithms to analyze the complex imaging data generated by DOCI. The researchers trained AI models to recognize subtle patterns in the imaging data and distinguish between different types of thyroid cancer, specifically papillary and follicular thyroid cancers, and to determine whether tissue was cancerous.The results were promising. The machine learning system showed strong agreement with pathological findings, accurately identifying cancerous regions within the tissue samples.“This is an exciting proof of principle demonstration that combining photonics with AI can work together and provide meaningful, reliable answers,” Vo-Dinh said. “The performance we’re seeing so far is very encouraging.”While the research is still in its early stages, the potential implications for patient care are significant.Because this approach directly analyzes the tissue and does not rely on waiting for lab-based assays, it could eventually support faster, point-of-care cancer assessment. Imagine a future where clinicians may be able to use similar tools directly on tissue, potentially even during surgery, to guide decisions in real time.“It could reduce the need for repeat biopsies and long waiting periods,” Vo-Dinh said. “And because the technique is non-invasive, it may also make screening easier and more accessible for patients.”The work underscores the critical importance of collaboration across institutions and disciplines, bringing together clinical expertise, advanced imaging, and data science.“This is a very synergistic partnership,” Vo-Dinh said. “Each group contributes something essential, from clinical insight to optical technology to computational analysis. That kind of complementarity is what drives innovation.”Next steps will focus on expanding and refining the technology, with the goal of enabling real-time, in situ cancer detection.“We’re excited to continue this collaboration and explore how far this approach can go,” Vo-Dinh said.
