First Axl inhibitor enters clinical trials

C Sheridan - Nature biotechnology, 2013 - go.gale.com
C Sheridan
Nature biotechnology, 2013go.gale.com
On June 19, BergenBio disclosed that BGB324, which it bills as a first-in-class Axl kinase
inhibitor, entered phase 1 clinical trials. The move marks an important milestone in the
emergence of a highly promising cancer target, which is involved in promoting cell survival
and metastasis. A new study urges caution, however, in the systemic administration of
inhibitors of Axl or a closely related tyrosine kinase, Mer, owing to their anti-inflammatory
activities, which, if abrogated, can lead to a more permissive environment for colon …
On June 19, BergenBio disclosed that BGB324, which it bills as a first-in-class Axl kinase inhibitor, entered phase 1 clinical trials. The move marks an important milestone in the emergence of a highly promising cancer target, which is involved in promoting cell survival and metastasis. A new study urges caution, however, in the systemic administration of inhibitors of Axl or a closely related tyrosine kinase, Mer, owing to their anti-inflammatory activities, which, if abrogated, can lead to a more permissive environment for colon cancer.
Axl and Mer are both members of the TAM receptor family, which also includes Tyro3, a kinase that is particularly abundant in the brain. All three are activated by a common ligand, Growth Arrest--specific protein 6 (Gas6), and they ordinarily play an embryonic developmental role in cell survival, migration and differentiation. High levels of Axl expression have been correlated with poor survival in many types of cancer, including breast cancer (Proc. Natl. Acad. Sci. USA 107, 1124-1129, 2010), acute myeloid leukemia (Amer. Soc. Hematol. Annual Meeting, San Diego 2011), glioblastoma multiforme (Clin. Cancer Res. 14, 130-138, 2008) and osteosarcoma (Biochem. Biophys. Res. Commun. 435, 493-500, 2013). In addition, activation of Axl kinase has been identified as one mechanism by which lung cancers can develop resistance to therapies targeting EGFR, such as Tarceva (erlotinib)(Nat. Genet. 44, 852-60, 2012).
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