Researchers at the VIB-UGent Center for Medical Biotechnology have discovered a promising strategy to improve treatment responses in multiple myeloma patients by blocking a protein that plays a key role in drug resistance. The study, published in Pharmacological Research, offers a potential new strategy to improve outcomes for patients whose disease has become less responsive to standard therapies.
Multiple myeloma (MM) is a type of blood cancer that affects the bone marrow. Patients are often treated with dexamethasone, a synthetic glucocorticoid frequently used in the clinic to regulate immune responses and slow cancer growth. However, as the disease progresses, many patients develop resistance to glucocorticoids.
The research team found that high levels of a protein, the chemokine receptor CCR1, are linked to worse outcomes in MM patients, particularly as the disease progresses. CCR1 is a receptor expressed on the surface of myeloma cells, through which the cells respond to chemical signals in the bone marrow environment and helps cancer cells to grow and survive.
Bert Luyckx, first author of the study, explains: "Our study shows that CCR1 is upregulated in MM patients with an unfavorable disease prognosis and plays a critical role in reducing glucocorticoid sensitivity in multiple myeloma cells. When we block CCR1 signaling, we see enhanced anti-cancer effects of dexamethasone in both lab models and patient samples."
The team used a CCR1 inhibitor called BX471 and found that it helped to restore the effects of dexamethasone in cells that had started to become resistant. The drug combination pushed cancer cells towards programmed cell death and disrupted proteins involved in drug resistance.
"By targeting CCR1, we were able to partially reverse glucocorticoid resistance in multiple myeloma cells," said Prof. Karolien De Bosscher. "This could offer new therapeutic opportunities for patients who no longer benefit from existing treatments."
The findings suggest that CCR1 inhibitors could be used alongside current treatments to enhance their effectiveness. Further research is needed to explore how this approach can be applied in clinical settings.
