University of South Florida and Moffitt Cancer Center

Most cells in our body go through a natural cycle of growth, division, maintenance and programmed cell death, also called apoptosis. While this ongoing cycle helps to maintain a balance of healthy cells in our bodies, alterations that result in uncontrolled cell growth are associated with the development of many diseases including cancer.

The Bcl-2 family of proteins consists of both pro- and anti-apoptotic proteins. By controlling the integrity of the mitochondrial membrane, these proteins maintain a homeostatic balance between cell growth and death. However, overexpression of the Bcl-2 protein is seen in many cancers and because it supports reduced cellular apoptosis, high levels of Bcl-2 are thought to promote therapeutic resistance that can contribute to poor prognosis.

Though much research is currently directed toward targeting Bcl-2 to reverse its contribution to drug resistance, a Rivkin Center pilot award recipient, Dr. Patricia Kruk, is examining the possibility of measuring levels of Bcl-2 as a biomarker for ovarian cancer and to improve early detection for ovarian cancer.

The Rivkin Center provided an award to University of South Florida researcher Dr. Patricia Kruk to investigate whether Bcl-2 could be detected in urine and whether elevated levels of urinary Bcl-2 were associated with ovarian cancer. Dr. Kruk says, We believe Bcl-2 overexpression may be an early change in the process of cellular transformation from normal to cancer. Therefore, we should be able to detect ovarian cancer with rising levels of urinary Bcl-2; this may be a key to early detection. To say Dr. Kruk’s results are exciting is an understatement.

Dr. Kruk looked at urine samples from 387 women from two separate tissue banks. She tested 77 samples from healthy controls, 161 with benign gynecologic disease and 149 with a mix of early and late stage ovarian cancer. She describes the results saying the amount of Bcl-2 was generally negligible in healthy control samples and low in women with benign gynecologic disease. In contrast, urinary levels of Bcl-2 in women with ovarian and primary peritoneal cancer were over 10 times that of healthy controls.

With Rivkin Center funding, Dr. Kruk also made a discovery she wasn’t expecting. In an initial analysis, a subset of normal and benign samples appeared to have curiously elevated urinary Bcl-2 levels. As the samples were blinded, meaning Dr. Kruk had no information about the women who provided the samples, she contacted Dr. Robert Bast, Jr. and his collaborators at the MD Anderson Cancer Center in Houston, Texas. Dr. Kruk told them, I’m getting unusual results for some women. What can you tell me about them? After they searched their database, their answer back to me was 8 of the 10 women are individuals at risk of developing ovarian cancer, either because of a family history, or a personal history with breast cancer. We don’t know yet what this means, but it’s possible Bcl-2 levels could be especially helpful at identifying women at increased risk for ovarian cancer.

The case for early detection of ovarian cancer is simple. Over 70% of women with ovarian cancer are diagnosed in the later stages when the prognosis is poor. According to Dr. Kruk and many others, to introduce an ovarian cancer screening test like the Pap smear for cervical cancer, or the mammogram for breast cancer, we must have a cost-effective, noninvasive test. For this reason, Dr. Kruk says, A simple urine test is absolutely ideal. Dr. Kruk’s results, with such a clear distinction between normal and cancerous samples, especially in such a noninvasive fluid such as urine, are tantalizing.

Dr. Kruk is aggressively pursuing this research. With the results from her Rivkin grant she is applying for additional funding from a variety of granting agencies and plans to expand the sample size and increase collaborations with researchers nationwide. She is also supporting the efforts of the University of South Florida in applying for patent review and licensing for the developing of the technology for clinical use. Dr. Kruk is full of praise for the Rivkin Center and says breakthroughs happen when a free exchange of ideas occurs, and the Rivkin Center is making this possible in ovarian cancer research.

Dr. Patricia Kruk, PhD