Chronic lymphocytic leukaemia (CLL) is one of the most common haematological diseases in older adults, with a higher incidence in men than in women. Despite advances in treatment, it remains an incurable disease, and patients eventually develop resistance to available therapies. In this context, a team of researchers led by Carlos Pipaón, from the Haematological Neoplasms and Haematopoietic Progenitor Transplantation group at the Marqués de Valdecilla Research Institute (IDIVAL), has published a study in the journal Cancers that could open new therapeutic avenues.
The article, titled “Distinct NF-kB Regulation Favors a Synergic Action of Pevonedistat and Laduviglusib in B-Chronic Lymphocytic Leukemia Cells Ex Vivo,” was authored by researchers Víctor Arenas, José Luis Castaño, Juan José Domínguez, Lucrecia Yáñez, and Carlos Pipaón. The study demonstrates that a combination of two drugs, Pevonedistat and Laduviglusib, can enhance the death of CLL tumour cells without severely affecting healthy cells.
A New Approach to CLL Treatment
Current treatments for CLL are designed to target specific characteristics of cancer cells, such as B-cell receptor signalling or the overexpression of the anti-apoptotic protein Bcl-2, which prevents cell death. However, these treatments are not curative and may lead to resistance over time.
The IDIVAL research group has focused on a lesser-explored aspect of CLL: proteostasis, the balance between protein synthesis and degradation within the cell. In CLL, this process is disrupted, promoting the production of proteins that drive tumour growth while degrading those that would control it.
Promising Results and Next Steps
The study has shown that Pevonedistat, a drug that blocks protein degradation, enhances the effect of Laduviglusib, an inhibitor previously shown to induce the death of leukaemic B lymphocytes. The combination appears to act synergistically and selectively on tumour cells, potentially minimising adverse effects on healthy cells.
Although these results were obtained from cultured blood samples of patients, the researchers plan to conduct further experiments in the coming months to assess its efficacy before considering clinical trials in humans. If the findings are confirmed, this combination could be added to existing treatments to prevent resistance and improve the prognosis of CLL patients.
“If we can ultimately demonstrate the effectiveness of this combined treatment in our preclinical trials, we would open the door to new therapies that could complement those currently available, helping to prevent the resistance that sometimes develops with prolonged use,” explains Carlos Pipaón.
Link to the article: https://pubmed.ncbi.nlm.nih.gov/39941899/
