SCIENTISTS DISCOVER POTENTIAL APPROACHES TO ENHANCE EXISTING CANCER THERAPIES
19 November 2003 - American Association for Cancer Research (AACR)

In a separate study, researchers presented an advanced imaging technique that may help physicians select which recurrent breast cancer patients are most likely to respond to hormonal therapy. The studies were presented today at the International Conference on Molecular Targets and Cancer Therapeutics organized by the American Association for Cancer Research, National Cancer Institute and European Organisation for Research and Treatment of Cancer in Boston.

In vitro and in vivo radiosensitization by p-aminobenzoic acid: Abstract 1005

A research team from New York University School of Medicine analyzed the effects of PABA and radiation alone and together on several cancer cell lines grown in laboratory dishes, as well as on implanted tumors in mice and chick embryos. In each of the experiments, they discovered that when PABA and radiation were administered together, tumor growth was substantially reduced compared to treatment with either radiation or PABA alone. In another set of experiments, they evaluated the ability of PABA to improve the effects of certain chemotherapy drugs. Again, the addition of PABA significantly improved the anti-tumor effects of drugs such as Taxol.

"These early findings suggest that PABA may optimize current cancer treatments by making tumor cells more vulnerable to certain chemotherapeutic drugs and radiation," says Peter Brooks, Ph.D., associate professor of radiation oncology and cell biology at NYU School of Medicine, who presented the results today. "We will continue to assess the cellular basis for PABA's effects."

Although it isn't yet clear how PABA acts, Dr. Brooks suspects that PABA might disrupt key growth control mechanisms in cancer cells as well as hamper their ability to repair DNA damage, thereby making these cells more vulnerable to radiation and chemotherapy. Based on the encouraging, preliminary results of the animal and cell-culture studies, PABA plus chemotherapy will be administered as part of a clinical trial at NYU.

Estrogen receptor imaging in breast cancer using [F-18]-fluoroestradiol PET: predicting the response of advanced disease to endocrine drug therapy by measuring regional target expression: Abstract 949

Imaging of estrogen receptors using F-18-fluoroestradiol positron emission tomography may predict the response of advanced breast cancer to endocrine therapy by measuring regional target expression. According to research done by Dr. David A. Mankoff, associate professor of radiology in the University of Washington School of Medicine, and his colleagues, imaging is ideally suited to quantify estrogen receptor expression because it avoids several factors that can make biopsy assays misleading in advanced disease.

It is known that breast tumors with high estrogen receptor expression are the most likely to respond to hormonal therapy. While receptor expression can be readily assessed with biopsied material, sampling errors may occur when patients have large or multi-site tumors. Furthermore, expression may change over time; recurrent breast cancer may have low or no estrogen receptor expression, even if the original primary tumor had high expression. These problems can be overcome using PET imaging to measure estrogen receptor expression at multiple sites and multiple times, reducing the risk of sampling errors.

Dr. Mankoff and colleagues investigated FES PET as a predictive test for patients with more advanced breast cancer treated by a variety of hormonal agents. So far, the results for 34 patients with a history of estrogen receptor positive tumors and recurrent or metastatic breast cancer have been analyzed. Over half of the patients had received prior adjuvant tamoxifen therapy and all had discontinued tamoxifen more than two months prior to the PET study, to prevent antagonism with the imaging agent. The participants in the study underwent FES PET close to the initiation of their therapy and subsequently received hormonal therapy without cytotoxic drugs for at least six months, unless there was clear tumor progression. More than 80 percent of the study participants were treated with aromatase inhibitors, which are being increasingly used in this patient population. Response was measured using clinical follow-up, tumor markers and a variety of other imaging studies. The responses were categorized as objective response, stable disease or progressive disease.

Qualitative imaging analysis of the FES PET studies showed that about 15 percent of patients had one or more FES-negative sites, suggesting loss of receptor. Only one of these patients responded to hormonal therapy. Quantitative image analysis showed that the level of FES uptake predicted response, with a significant association between FES uptake and subsequent response to hormonal therapy. No patient with low FES uptake had an objective response.

Dr. Mankoff said that these early results show the promise of FES PET for selecting breast cancer patients for hormonal therapy. Up to now, PET imaging has been used largely to help define the extent of tumor spread. This study is an example of how PET imaging can be used to assess specific targets for cancer treatment, with immediate applications to drug therapy trials and to patient care.

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