NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
April 13, 2004 • Volume 1 / Number 15 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Technique Detects Cancerous Cells' Metabolic "Fingerprints"

Using a newly developed technique of proton magnetic resonance spectroscopy for intact tissue analysis, researchers from Harvard University were able to analyze tissue samples and find metabolic "fingerprints" of prostate cancer cells - chemical signatures that also appear to be indicative of a tumor's aggressiveness. Reporting at the American Association for Cancer Research (AACR) annual meeting, Dr. Leo L. Cheng discussed the NCI-funded study, which used the new spectroscopy technique on 199 tissue samples from approximately 82 patients who had undergone prostatectomy. Results were compared to standard histopathological assessments conducted on the samples after spectroscopy study.

Overall, only 20 samples were cancerous, as defined by histopathology. Using this new technique, the researchers were able to obtain accurate metabolite measurements and, based on principal component analysis of spectroscopy data and correlation with histopathology measurements (by linear regression analysis), could identify cancerous and noncancerous tissues from the same patient. More importantly, levels of metabolic markers could be correlated with the patient's clinical status, such as the overall pathological features and stage of disease (according to the AJCC staging system).

Dr. Cheng observed that such research could eventually have important implications for patients, who often have to undergo multiple biopsies to confirm that they have prostate cancer. The histopathology of a sample can look normal, he said, "but the chemistry may not be normal. If we can establish the markers, we will find more cancers." This could prevent the need for multiple biopsies, he added, but potentially allow for early identification and treatment of more aggressive prostate cancers.

Tamoxifen and Estrogen Receptor Status in Breast Cancer

A new study shows that the estrogen receptor (ER) status of a primary breast cancer is associated with the ER status of subsequent cancer in the opposite, or contralateral, breast in patients not receiving tamoxifen treatment. NCI's Dr. Sandra Swain and colleagues published the report in the April 7 issue of the Journal of the National Cancer Institute.

About two-thirds of all breast cancer cells contain significant levels of receptors for the female hormone estrogen; these cancers are called ER-positive and the others are called ER-negative. ER-positive tumors tend to grow less aggressively than ER-negative tumors and are associated with a better prognosis for patients. Previously, tamoxifen treatment has been shown to reduce the risk of contralateral breast cancer by approximately 30 to 50 percent.

The current study analyzed data from three clinical trials. ER data were available for only 110 patients who developed contralateral breast cancer. Among those patients not receiving tamoxifen, almost 90 percent had both ER-positive primary and contralateral breast cancer and 70 percent had both ER-negative primary and contralateral breast cancer. "The association between the ER status of the primary cancer and the contralateral breast cancer was modest and did not reach statistical significance," according to the authors. "

The use of tamoxifen by women aged 50 years and older who had an ER-positive primary cancer appeared to reduce the risk for developing ER-positive contralateral breast cancer," said Dr. Swain. "It cannot be definitively concluded that tamoxifen provides no reduction in risk of a contralateral breast cancer for patients with an ER-negative primary cancer because of the small number of patients in the current sample and in the world literature. However, if there is a benefit it is marginal."

Tumor Growth Inhibited in Rare Thyroid Cancer

As reported at a press conference at the AACR meeting, Drs. John Copland and Robert Smallridge of the Mayo Clinic in Jacksonville, Fla., have been working with a small-molecule drug candidate shown to inhibit tumor growth up to fourfold in anaplastic thyroid cancer, a very rare and highly aggressive type of thyroid cancer. This type of cancer accounts for only one percent of all thyroid cancers but has a very poor prognosis: 90 percent of patients die within one year of diagnosis. This type of cancer does not respond to any known treatment.

Sankyo Company researchers discovered the drug candidate, RS-5444, in a screen for antitumor activity and then sought the help of specialists at the Mayo center to further study its properties. The molecule works by activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) - a nuclear receptor that activates genes involved in a wide range of cellular processes, including apoptosis, cell-cycle control, carcinogenesis, and inflammation.

PPAR-γ is a particularly attractive drug target because it has been implicated as a tumor suppressor in several human cancers. Additionally, mutations and deletions in the PPAR-γ gene have been found in other types of thyroid cancer but not in anaplastic thyroid cancer. RS-5444 tightly binds and activates PPAR-γ, which negatively regulates the cell cycle and triggers apoptosis in a p53-independent manner. The drug has shown both antitumor and chemopreventive effects in cancer cell lines and animal models but, as of yet, no clinical trials are testing the drug's efficacy in humans.

Progesterone Receptor Antagonist Inhibits Breast Cancer in Rats

At a press conference at AACR's annual meeting, Dr. Jens Hoffman of Schering AG, a German pharmaceutical company, announced recent results of the company's work with a novel progesterone receptor inhibitor that shows strong activity against breast cancer in rats.

The progesterone receptor is a transcription factor that, upon binding the steroid hormone progesterone, enters the nucleus of cells and affects the transcription of genes involved in cell proliferation.

In rodent tumor cell models, the novel drug demonstrated strong antiproliferative activity and also provided protection against carcinogen-induced breast cancer. It appears to work via multiple mechanisms distinct from those of the antiestrogen drug tamoxifen and aromatase inhibitor Arimidex; it not only stops cells from growing and dividing but also appears to induce apoptosis and cell death. Apoptosis may be triggered when the drug blocks upregulation of the epidermal growth factor receptor (EGFR). The company is currently testing the drug in early-phase clinical trials.