BTK (Bruton's Tyrosine Kinase)
Key signaling kinase downstream of MYD88
- Expression
- Constitutively activated
- Evidence level
- established
- Targeted by
- Ibrutinib, Zanubrutinib, Pirtobrutinib
Role in pathogenesis
BTK is a non-receptor tyrosine kinase recruited to the Myddosome complex by mutated MYD88. It activates NF-kB pro-survival signaling independently of IRAK4/IRAK1. BTK also participates in B-cell receptor signaling. It is the direct target of ibrutinib and zanubrutinib, the most effective WM therapies.
Targeting drugs (3)
| Drug | Mechanism | Response | Line |
|---|---|---|---|
| Zanubrutinib | Second-generation selective BTK inhibitor | ~95% ORR; 36% VGPR+CR | 1st |
| Ibrutinib | First-generation BTK inhibitor | 90% ORR; 73% MRR (previously treated) | 1st |
| Pirtobrutinib | Non-covalent (reversible) BTK inhibitor | ~68% ORR (after covalent BTKi); 56% VGPR with venetoclax combo | 2nd |