Brigatinib and Its Combination with INK-128 as a Novel Treatment for NF2-Deficient Meningiomas
Abstract
Presently, an FDA-approved medical therapy for NF2-deficient meningiomas is not available. To identify a novel therapy for these tumors, we, as members of the Synodos for NF2 Consortium, in collaboration with the National Center for Advancing Translational Sciences (NCATS), identified brigatinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, to be effective as a single agent in inhibiting proliferation of NF2-deficient meningioma cells and suppressing tumor growth in an orthotopic NF2-deficient meningioma mouse model. Additionally, INK128, a dual mTORC1/2 inhibitor, synergized with brigatinib to suppress meningioma cell proliferation in vitro. Based on these data, we have proposed to evaluate the brigatinib/INK128 combination as an effective treatment for NF2-deficient meningiomas and investigate their mechanisms of action. We have found that NF2-deficient meningiomas did not express ALK. Brigatinib suppressed the growth of NF2-deficient tumors via inhibition of multiple receptor tyrosine kinases (RTKs) and non-RTKs, such as focal adhesion kinase (FAK). These findings have led to a phase II clinical trial to evaluate brigatinib in patients with NF2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1213982
Entities
People
- Long-Sheng Chang
Organizations
- Nationwide Children's Hospital