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Targeting Bcl-2/Bcl-XL induces antitumor activity in uveal melanoma patient-derived xenografts.


ABSTRACT:

Purpose

Uveal melanoma (UM) is associated with a high risk of metastases and lack of efficient therapies. Reduced capacity for apoptosis induction by chemotherapies is one obstacle to efficient treatments. Human UM is characterized by high expression of the anti-apoptotic protein Bcl-2. Consequently, regulators of apoptosis such as Bcl-2 family inhibitors may constitute an attractive approach to UM therapeutics. In this aim, we have investigated the efficacy of the Bcl-2/Bcl-XL inhibitor S44563 on 4 UM Patient-Derived Xenografts (PDXs) and derived-cell lines.

Experimental design

Four well characterized UM PDXs were used for in vivo experiments. S44563 was administered alone or combined with fotemustine either concomitantly or after the alkylating agent. Bcl-2, Bcl-XL, and Mc

SUBMITTER: Nemati F 

PROVIDER: S-EPMC3890263 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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