Startup’s Trojan Horse Therapy Attacks Aggressive Cancers, Spares Healthy Cells
By harnessing a precise delivery mechanism, the research team's novel treatment ensures that the radioactive payload reaches only the cancer cells, significantly improving safety and reducing toxicity.
March 19, 2025 I By Dave DeFusco
In a pioneering approach to cancer treatment, a North Carolina startup—dGenThera—has developed a targeted radiotherapeutic based on astatine-211, an alpha-emitting isotope. This technology could reshape the landscape of targeted radiotherapeutics and provide new hope for patients battling aggressive cancers.
“Targeted radiotherapeutics based on astatine-211 destroys tumors while sparing healthy tissues,” said Dr. David Nicewicz, a company co-founder and William R. Kenan, Jr. Distinguished Professor at UNC-Chapel Hill. “By harnessing a precise delivery mechanism, our novel treatment ensures that the radioactive payload reaches only the cancer cells, significantly improving safety and reducing toxicity.”
Traditional chemotherapy, despite its effectiveness, often causes severe side effects due to its non-selective nature. Astatine-211, the core isotope in the company’s approach, induces double-stranded DNA breaks in cancer cells, leading to cell death. Unlike traditional targeted radiotherapeutics (TRTs) that rely on metal radionuclides requiring bulky chelation cages—molecular structures that bind to metal atoms—the company’s small molecules can freely cross the blood-brain barrier.
“This makes them potentially more effective for treating gliomas and brain metastases, offering new hope for patients with hard-to-treat brain cancers,” said Dr. Li Zibo, a joint professor in the departments of Chemistry and Radiology and director of the Cyclotron & Radiochemistry Research Program in the UNC School of Medicine.
In their initial breast cancer xenograft study, the researchers—Drs. Nicewicz, Zibo Li and dGenThera’s co-founders, Dr. Anthony Casarez, chief scientific officer, and Dr. Louis Metzger, chief executive officer, successfully treated mice with a single dose of their astatine-211-based TRT. The results were striking: Complete tumor control for 28 days; some tumors completely disappeared; and mice showed only a temporary drop in body weight before full recovery.
“The speed of our preclinical success with such limited financial resources is quite remarkable and has laid the foundation for the company’s next steps,” said Dr. Casarez, “which are securing venture capital, scaling up research and advancing toward clinical trials. Our rapid progress should provide investors with complete confidence in our operational execution.”
Many companies, like Novartis, BMS and Eli Lilly, have invested a lot in cancer treatments using actinium-225, however dGenThera is developing treatments based on astatine-211. Actinium-225 goes through multiple decay steps, which can cause tiny radioactive particles to break free and harm healthy tissues. In contrast, astatine-211 only goes through one decay step before becoming stable, reducing the risk of extra radiation exposure.
This means fewer unintended effects on healthy tissues, making it potentially safer than existing TRTs. Astatine-211’s ability to form chemical bonds helps keep it more stable than metal-based radionuclides. This makes it an ideal candidate for treating glioblastomas and other brain tumors.
The production of astatine-211 starts with bismuth-209, an abundant element found in everyday products like Pepto-Bismol. Unlike other radionuclides that rely on scarce or geopolitically sensitive materials—actinium-225 is made from radium-226 which exists in trace quantities in the earth’s crust, and lutetium-177 is made from ytterbium-176, which is primarily mined in Russia–astatine-211 can be synthesized in commercial cyclotron facilities worldwide, ensuring stable and cost-effective production.
dGenThera uses a smart delivery method similar to a “Trojan horse” strategy. Cancer cells, which consume nutrients faster than healthy cells, unknowingly absorb the radiotherapeutic agent disguised as a nutrient. This targeted approach ensures the treatment attacks only cancer cells, sparing healthy tissue. Early safety tests in mice showed no fatalities, and the animals quickly regained weight, suggesting the treatment could have minimal side effects in humans.
The company emerged from research into positron emission tomography (PET) imaging agents. These diagnostic tools allowed scientists to track where a molecule travels in the body. Now, by swapping a single atom in their PET imaging agents, the team has transformed them into potent therapeutic compounds—what are called “theranostic agents” (therapeutic + diagnostic).
“This means that before administering a therapeutic dose, doctors can use a PET scan to confirm that the drug will reach its intended target, making treatments more precise and predictable,” said Dr. Metzger. “This may enable a faster clinical development trajectory than for other types of investigational cancer therapeutics, and allow us to quickly bring efficacious treatments to patients for whom current standard of care does little to extend survival and improve quality of life.”
The company is currently raising venture capital to fund further development. The first step in a three-year trial, which will cost upwards of $20 million, will be testing its diagnostic imaging agents in humans, a low-risk process that will confirm tumor selectivity. Since the targeted nutrient transporter is 90% conserved between mice and humans, the transition to clinical trials is expected to be smoother than for many other novel cancer treatments.
Once diagnostic studies confirm the treatment’s selectivity, the first phase of therapeutic trials will commence. dGenThera plans to prioritize three of the most aggressive and lethal cancers: Triple-negative breast cancer, pancreatic cancer (PDAC) and glioblastoma.
“Once regulatory hurdles are cleared, astatine-211 could become the gold standard in next-generation radiotherapeutics,” said Dr. Nicewicz.