March 15 Cancer Research Highlights

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Selected Articles from the March 15, 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 Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the March 15 issue of Cancer Research.

Winning the War against Cancer: From Genomics to Bedside and Back,
a Tribute to George F. Vande Woude

Award-winning cancer researcher George F. Vande Woude’s 70th birthday was marked by the 2006 Scientific Symposium Winning the War Against Cancer: From Genomics to Bedside and Back, held September 10-12, 2006 at the Van Andel Research Institute in Grand Rapids, Michigan. Meeting participants took this opportunity to reflect on Dr. Vande Woude’s many and significant contributions to cancer research over the past quarter century.

mTOR Inhibition Delays Ovarian Cancer in a Mouse Model

Early intervention strategies are urgently needed for women predisposed to ovarian cancer. The mammalian target of rapamycin (mTOR) is frequently deregulated in ovarian carcinomas, resulting in disrupted translation of cancer-related mRNAs involved in cell proliferation, invasion, and angiogenesis. Mabuchi et al. showed that early intervention with an mTOR inhibitor markedly delayed tumor onset, ascites formation, and peritoneal dissemination in an ovarian cancer mouse model exhibiting activated mTOR. Moreover, expression of MMP-2 and VEGF was diminished, consistent with decreased invasiveness and angiogenesis, respectively. Thus, mTOR inhibition shows promise as a chemopreventive strategy in women with a high familial risk of ovarian cancer.

PTP1B Deficiency Protects against HER2-Positive Breast Cancer

The protein tyrosine phosphatase PTP1B is a well-established metabolic regulator and is a leading target for the treatment of diabetes and obesity. However, PTP1B is expressed ubiquitously and, because it negatively regulates several tyrosine kinase receptors in cell lines, there had been concern that PTP1B inhibition might contribute to cancer.  By studying crosses between PTP1B knockout mice and transgenic mice overexpressing the known breast cancer oncogene HER2/Neu, Bentires-Alj et al. showed that PTP1B deficiency actually protects against or significantly delays the onset of HER2/Neu–evoked mammary tumors. These findings identify PTP1B as a potential target for breast cancer prevention and/or therapy.

Functional, Tumor-Specific T Cells Generated from Hematopoietic Stem Cells

Adoptive cell transfer of tumor-reactive lymphocytes has been demonstrated to be an effective treatment for cancer patients. In this study, Zhao et al. genetically modified human umbilical cord blood–derived hematopoietic stem cells (HSCs) and demonstrated that human HSCs can be transduced with retroviral vectors expressing anti-tumor antigen T-cell receptors and that T cells developed in vitro recognize human tumor antigens. The further development of this approach raises the possi­bility that transplantation of retrovirally transduced in vitro developed T cells in the setting of adoptive immunotherapy in cancer patients may be therapeutically useful.

DKK1 Is a Novel Biomarker for Human Cancer

A number of biomarkers for cancer therapy have been reported; however, no tumor marker has been sufficiently useful for detection of most types of cancers at a potentially curative stage. Yamabuki et al. demonstrated that Dikkopf-1 (DKK1) overexpression was observed in the vast majority of lung and esophageal cancers and was associated with poor clinical outcome. Serum DKK1 levels were elevated in the sera of 70% of lung and esophageal cancer patients. The use of both DKK1 and CEA/ProGRP increased sensitivity to detect lung cancers up to 90%. DKK1 should be useful as a novel diagnostic/prognostic biomarker in the clinic.