Desarrollo de micropartículas de dexametasona como estrategia para aumentar la eficacia de los esquemas de poliquimioterapia

Abstract

Glucocorticoids (GCs) and dexamethasone play a central role in the treatment of lymphoid malignancies, particularly acute lymphoblastic leukaemia (ALL). Preclinical studies have shown that GCs also affect cell differentiation, proliferation and apoptosis of osteosarcoma cells, hepatoma cells, mammary tumor cells, glioma cells, melanoma cells and thyroid cancer cells. The proliferation and apoptotic effects of GCs are cell type-specific as well as time and concentration dependent. In spite of the high effectiveness of dexamethasone treatment in ALL, mainly in children, GC resistance occurs in 10-30% of untreated patients, being more frequent in T-lineage than B-precursor acute lymphoblastic leukaemia. Furthermore, systemic administration of high doses of dexamethasone are required for inducing tumor cell apoptosis but causes severe side effects such as osteoporosis, Cushing's syndrome or an increased risk of infections. Even though most combined chemotherapy protocols currently used in clinics include dexamethasone at high doses, recent clinical investigations on the eficacy of dexamethasone in refractory multiple myeloma have shown synergic effects of low doses of this GC combined with pomalidomide or lenalidomide...