Strategies for overcoming resistance to Bruton's tyrosine kinase inhibitor zanubrutinib.
Hematol Oncol
; 42(4): e3294, 2024 Jul.
Article
de En
| MEDLINE
| ID: mdl-38847437
ABSTRACT
Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment of B-cell malignancies. They target BTK, a key effector in the B-cell receptor (BCR) signaling pathway, crucial for B-cell survival and proliferation. The first-in-class irreversible BTK inhibitor, ibrutinib, was approved for various B-cell malignancies but has limitations due to off-target effects. Second-generation inhibitors, such as acalabrutinib and zanubrutinib, offer improved selectivity and reduced side effects. However, resistance to BTK inhibitors, driven by BTK mutations, remains a challenge. Combinatorial therapies with PI3K inhibitors, immune checkpoint inhibitors, BH3 mimetics, and anti-CD20 antibodies show promise in overcoming resistance. Noncovalent BTK inhibitors and proteolysis-targeting chimeras (PROTACs) are emerging strategies with potential to combat resistance. Overall, advancements in BTK-targeted therapies provide hope for improved outcomes in patients with B-cell malignancies and a promising avenue to address drug resistance. Further research is needed to optimize combination therapies and identify optimal treatment regimens.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pipéridines
/
Pyrazoles
/
Pyrimidines
/
Résistance aux médicaments antinéoplasiques
/
Inhibiteurs de protéines kinases
/
Agammaglobulinaemia tyrosine kinase
Limites:
Humans
Langue:
En
Journal:
Hematol Oncol
Année:
2024
Type de document:
Article
Pays d'affiliation:
République tchèque