Thursday, October 25, 2012
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Anaplastic lymphoma kinase (ALK); nucleophosmin (NPM1; B23); platelet derived growth factor receptor A
(PDGFRA; PDGFR2; CD140A); PDGFRB (PDGFR1; CD140B)
Studies in mice and in a
single patient suggest inhibiting PDGFR2 could help treat anaplastic large
cell lymphomas driven by the NPM1-ALK oncoprotein. In a mouse model of
NPM1-ALK-driven anaplastic large cell lymphoma, inhibition of Pdgfr1 with Gleevec imatinib decreased
tumor mass and increased survival compared with no treatment. In the mouse
model, imatinib plus the ALK inhibitor Xalkori crizotinib caused
greater tumor growth inhibition than either compound alone. In a single
relapsed, chemotherapy-refractory patient, imatinib led to PDGFR1 levels that
were lower than those before treatment and led to complete clinical
remission. Next steps include designing a clinical trial to test imatinib in
additional patients with NPM1-ALK-driven lymphomas and studying the role of
PDGFR2 on the tumor microenvironment.
Novartis AG markets the
BCR-ABL tyrosine kinase
inhibitor Gleevec to treat chronic myelogenous leukemia (CML) and
gastrointestinal stromal tumors.
Pfizer Inc. markets
Xalkori to treat non-small cell lung cancer (NSCLC). The drug also is in
Phase I testing to treat solid tumors.
Published online Oct. 25, 2012
Patented; licensed to Akron Molecules GmbH
Laimer, D. et al. Nat.
Med.; published online Oct. 14, 2012;
Contact: Lukas Kenner, Medical University of Vienna, Vienna,
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