April 1 Clinical Cancer Research Highlights

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Selected Articles from the April 1, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the April 1 issue of Clinical Cancer Research.

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Phase I Study of PX-12 Shows Promise

Ramanathan et al.
Page 2109

Thioredoxin-1 (Trx-1) is a cellular redox protein that promotes tumor growth, inhibits apoptosis, and up-regulates hypoxia-inducible factor-1α and vascular endothelial growth factor. Objectives of this study were to determine safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of PX-12, a small-molecule inhibitor of Trx-1. PX-12, the first Trx-1 inhibitor to enter clinical trials, was tolerated up to a dose of 226 mg/m² by 3-h infusion. Based on PD and PK data, a trial of  prolonged infusion schedule of PX-12 has been initiated.

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CNTO 95 Well Tolerated in Patients

Mullamitha et al.
Page 2128

A fully human monoclonal antibody to anti-αv integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. Mullamitha et al. assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors. CNTO 95 was generally well tolerated. Six patients received extended therapy, including one patient with a prolonged response. Biopsy data confirmed tumor localization and pharmacodynamic activity.

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Gene Expression Markers Predict Tipifarnib Response  

Raponi et al.
Page 2254

The orally available farnesyltransferase inhibitor (FTI) tipifarnib has demonstrated clinical efficacy in hematological disease. Utilizing microarray technology to identify gene expression markers that increase the likelihood of response to tipifarnib, Raponi et al. found that increased expression of the guanine nucleotide exchange factor AKAP13 correlated with resistance to the FTI. Identifying such gene expression markers is an important step toward defining diagnostic signatures that could be used to identify acute myelogenous leukemia (AML) patients who are likely to respond to tipifarnib and for understanding pathways that are affected by farnesyltransferase inhibition in AML.

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Molecular Studies Provide Evidence for Ayurvedic Medicine

Widodo et al.
Page 2298

Ayurveda, a 5,000-year-old system of medicine originating in India, emphasizes prevention of disease and rejuvenation of body systems. However, there have not been enough molecular studies to provide insights into its effects. Widodo et al. reported the selective killing of cancer cells by leaf extract of ashwagandha (an important herb in Ayurveda) and also isolated a component responsible for this effect. The molecular basis of cancer-cell killing was related to preferential activation of wild type p53 function in cancer cells and presents a potential tool for safe cancer therapeutics.

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