Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.

ABSTRACT:

Background

Zalypsis(®) is a marine compound in phase II clinical trials for multiple myeloma, cervical and endometrial cancer, and Ewing's sarcoma. However, the determinants of the response to Zalypsis are not well known. The identification of biomarkers for Zalypsis activity would also contribute to broaden the spectrum of tumors by selecting those patients more likely to respond to this therapy.

Methods

Using in vitro drug sensitivity data coupled with a set of molecular data from a panel of sarcoma cell lines, we developed molecular signatures that predict sensitivity to Zalypsis. We verified these results in culture and in vivo xenograft studies.

Results

Zalypsis resistance was dependent on the expression levels of PDGFRα or constitutive phosphorylation of c-Kit,

SUBMITTER: Moneo V 

PROVIDER: S-EPMC4023704 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature