UACC researchers prepare for AACR Annual Meeting

UACC researchers prepare for AACR Annual Meeting

Several dozen University of Arizona Cancer Center researchers are presenting the efforts of their work displayed on 30 posters at the AACR Annual Meeting in Chicago.

The American Association for Cancer Research was founded in 1907 by a group of 11 physicians and scientists interested in research to further the investigation and spread the knowledge of cancer. The organization has 34,000 members.

Some of the UA Cancer Center’s research highlights include:

• Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study

Endometrial cancer is the most common gynecologic cancer diagnosis in the United States, accounting for an estimated 40,100 new cases and 7470 deaths in 2008. In this study, women with a precancerous lesion known as AEH (atypical endometrial hyperplasia) were evaluated by karyometric analysis of the cell nuclei from hysterectomy tissue specimens. Karyometry is based on a quantitative assessment of the cells nuclear chromatin pattern using digital image analysis. This method can detect very early cellular events in the process of carcinogenesis.022.JPG

Karyometry showed that although the nuclei of both AEH and type I endometrial cancer are very similar, there were enough differences in the percentage of abnormal nuclei in these lesions to help define objective criteria in the distinction between AEH and cancer. These findings suggest that Karyometry may serve as a method to measure risk for the development of invasive cancer from AEH.

• A pilot clinical study of limonene in women with early stage breast cancer

Limonene is a bioactive component found in citrus peel oil that has demonstrated anticancer properties in preclinical studies. The purpose of this study was to evaluate whether limonene and its primary metabolite perillic acid (PA) would distribute extensively to the breast tissue and reach an effective drug concentration. Secondary endpoints included evaluation of changes in cancer-related biomarkers in plasma and tissue.025_0.JPG

The study of 40 women with early-stage breast cancer who were administered limonene orally for two to six weeks indicated that limonene was found to concentrate in breast tissue rather than in serum (blood) and resulted in minimal changes in systemic biomarkers. PA did not concentrate in breast tissue. The limonene intervention did result in a significant decrease in the cancer-related marker, cylclinD1, in tumor tissue.

Exploratory profiling of metabolites in plamsa (metabolomics) indicate that there were 26 unknown metabolite makers in serum that also significantly changed with limonene intervention. Identification of those markers in order to determination their relation to breast cancer is ongoing. Further clinical trials with longer intervention are necessary to establish limonene's potential role as a chemopreventive role in breast cancer.

• Vorinostat abrogates ridaforolimus-induced activation of Akt in synovial sarcoma cells: A possible rationale for their synergism

Soft-tissue sarcoma is a relatively rare disease, with approximately 10,000 new cases diagnosed per year in the United States. Soft-tissue sarcoma is a diverse disease, consisting of more than 50 different histological subtypes. This group of diseases kills about 4,000 people every year in the U.S.

Unresectable or metastatic disease occurs in approximately 40 to 60 percent of soft-tissue sarcoma patients, which portends a very bad prognosis. There are no curative treatment options for soft-tissue sarcoma patients yet. The first-line therapy is doxorubicin, which yields a response rate of only 26 percent.

033_0.jpgThe research project focuses on a specific subtype of soft-tissue sarcoma called synovial sarcoma. The goal is to identify promising new treatment options to treat this disease. Researchers tested a number of drugs alone and with one another in the lab to identify an effective combination to kill these cancer cells.

A number of promising drug combinations were identified that are synergistic in stopping sarcoma cells from growing and dividing. Efforts were focused on one unique combination of two drugs, ridaforolimus (inhibits a protein called mTOR) and vorinostat (inhibits a class of enzymes called histone deacetylases). This combination also proved effective in a panel of different cell lines, including osteosarcoma, melanoma, pancreatic cancer and non-small cell lung cancer.

In addition, an investigation of the molecular mechanisms through which these drugs work has begun and plans call for testing the effectiveness of this drug combination in the clinic in the near future.

April 4, 2012