Scientists at the University of Cambridge have identified a promising new drug combination that could improve outcomes for patients with B-cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer. This breakthrough has the potential to reduce reliance on toxic chemotherapy, particularly for older patients who tend to have poorer survival rates.
Each year, more than 500 people in the UK are diagnosed with B-ALL. For young patients, current treatments require over two years of chemotherapy—an aggressive regimen that can cause serious side effects, including infections, bruising, hair loss, and long-term damage to nerves, joints, and the heart. While survival rates in younger children remain high, older children and adults face a much tougher prognosis.
“Every week, I see adult patients battling this aggressive leukemia,” said Dr. Simon Richardson from the Cambridge Stem Cell Institute. “Chemotherapy can cure many, but its side effects are severe. We need treatments that are kinder and more effective.”
Existing B-ALL treatments focus on destroying malignant B cells—immune system cells that accumulate excessively in leukemia and interfere with healthy blood production.
Cancer drug shows promise in HIV cure research
Dr. Richardson and Professor Brian Huntly’s team explored a new approach using two oral drugs: venetoclax and inobrodib.
- Venetoclax is already used for acute myeloid leukemia (AML) and triggers cell death via the BCL2 protein. However, it is not consistently effective in B-ALL.
- Inobrodib, developed by CellCentric, inhibits a gene called CREBBP, altering how B-ALL cells process fats. When paired with venetoclax, this disruption causes cancer cells to die through ferroptosis—a different, more aggressive form of cell destruction.
Crucially, this combination was effective against drug-resistant leukemia cells, making it a potential game-changer for patients who fail standard treatments.
New method for controlled-release makes cancer drugs less toxic to healthy tissues
Professor Huntly emphasized the importance of moving to clinical trials: “These results are auspicious. While our study was in mice, we’re optimistic about seeing similar effects in patients. Since venetoclax and inobrodib have already been tested together in AML trials, we know they are safe.”
Unlike CAR-T therapy, which can permanently eliminate B-cells from the body, this drug combination allows normal immune function to return once treatment stops, potentially offering a safer, more accessible option.
Additionally, as venetoclax is expected to become more affordable in the coming years, this approach could provide an effective, cost-efficient alternative to existing treatments.
Journal Reference:
- Garcia-Gimenez, A., Ditcham, J.E., Azazi, D.M.A. et al. CREBBP inactivation sensitizes B cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition. Nat Commun 16, 4274 (2025). DOI: 10.1038/s41467-025-59531-6
