Inhibitor of novel cancer target, LPAAT-beta, demonstrates selective anti-cancer effects

November 21, 2002

Frankfurt, Germany--In a plenary session at the Symposium on Molecular Targets and Cancer Therapeutics, Dr Jack W. Singer, M.D. and Research Program Chairman of Cell Therapeutics, Inc. (CTI) today (Thursday 21 November) presented data from preclinical studies on a novel cancer target LPAAT-beta[1] in cultured cells and in preliminary animal models.

Through preclinical studies, CTI scientists found that LPAAT-beta is highly expressed in cancers of the lung, ovary, prostate, bladder, cervix and brain but is minimally expressed in most normal tissues. When LPAAT-b was over expressed in cell lines, they became more tumorigenic and this change was reversed when the over-expressed gene was removed. When LPAATb expression was decreased in tumor cells by a genetic technique known as RNAi, their proliferation decreased. CTI scientists also developed small molecule inhibitors specific to LPAAT-b and these compounds induce apoptosis (cell death) in a wide variety of tumor cell lines. When nude mice bearing HT-29 colon cancer were treated with the compound, it delayed tumor growth significantly without producing toxicities. Similar results were achieved with related compounds in mice with Lewis lung cancers or NCI-H460 human lung cancers.

"These data affirm what we had previously noted in our initial studies - that the enzyme LPAAT-b produces a cofactor for signalling pathways that may be essential to cancer cell growth and viability and the inhibition of this enzyme causes cancer cells to die," Dr Singer told a news briefing today (Thursday 21 November) at the EORTC-NCI-AACR[2] Symposium on Molecular Targets and Cancer Therapeutics.

He added: "The experiments in animal models show that the small molecule LPAAT-b inhibitors can effectively kill tumor cells without having pronounced effects on normal cells."
-end-
Notes:

[1] LPAAT-beta is an enzyme, initially cloned by CTI scientists, that regulates the production of a lipid known as phosphatidic acid (PA) that is thought to be critical in the activation of several key oncologic pathways, including the RAS/RAF/ERK pathway and the AKT/mTOR pathway.

[2] EORTC [European Organisation for Research and Treatment of Cancer; NCI [National Cancer Institute]; AACR [American Association for Cancer Research].

Cell Therapeutics, Inc. website: www.cticseattle.com.

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European Organisation for Research and Treatment of Cancer

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