In a groundbreaking development at the Precision Medicine World Conference (PMWC) 2025, researchers have unveiled promising advances in targeting the "dark genome" to combat cancer progression, with particular focus on a novel therapeutic approach using ADAR1 inhibition.
Dr. Catriona Jamieson, Chief of the Division of Regenerative Medicine at UCSD Health Moores Cancer Center, presented compelling findings on how stress-activated base editors contribute to cancer development and potential recurrence. The research highlights a critical intersection between natural cellular processes and innovative therapeutic strategies.
Understanding the Dark Genome and Base Editing
The research team identified crucial differences between human and mouse models, particularly in stress-response mechanisms. "We have primate-specific editing enzymes that are activated in response to stress and viral infections," explained Dr. Jamieson. These APOBEC enzymes, ranked as the second most common signature across all cancers, introduce specific mutations in response to stress and inflammatory conditions.
Space Research Reveals Critical Insights
Through collaborative studies with NASA and commercial space missions, researchers examined the effects of space-related stress on cellular mutations. Analysis of astronaut samples from Axiom Missions 2 and 3 revealed striking results.
"After 21 days in space, all astronauts had mutations," Dr. Jamieson reported. "These expanded, mutated progenitor clones became hypersensitive to inflammatory growth factor signaling and could activate ADARp150, a malignant regenerating gene."
Rebecsinib: A First-in-Class Treatment Approach
The research has led to the development of rebecsinib (17S-FD-895), a pioneering small molecule inhibitor of ADAR1. This therapeutic candidate, developed by Aspera Biomedicines, shows remarkable potential in preventing cancer cell self-replication.
Using a sophisticated cancer and aging stem cell nanobioreactor system, researchers demonstrated rebecsinib's ability to:
- Stop cancer cells from self-replication
- Prevent metastatic progression
- Reverse ADAR-activated cancer regeneration
Accelerated Testing in Space
The International Space Station provided an optimal environment for testing rebecsinib's efficacy. "It just happens faster in space," noted Dr. Jamieson. The research team, working with ISS National Labs and NASA, observed the drug's ability to function as a cancer kill switch under extreme conditions.
Future Implications
The research team is preparing to submit an investigational new drug application for rebecsinib. This breakthrough could potentially impact treatment approaches across 20 different cancer types where ADAR1p150 activation has been identified.
"We think ADAR1p150 is an important target, and we'll be able to do this in all of us soon, with just 10 mL of blood and a little bit of tumor," Dr. Jamieson concluded, highlighting the potential for personalized treatment approaches.
