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Leszek Kotula, MD, PhD, an associate professor of urology, biochemistry and molecular biology, stands in his lab at Upstate Medical University.

Upstate professor publishes paper on how common gene may influence aggressive prostate cancer

An Upstate Medical University professor published a study this week in an international journal this week, addressing a breakthrough discovery of how a common gene may affect aggressive prostate cancer.

Leszek Kotula, MD, PhD, an associate professor of urology, biochemistry and molecular biology at Upstate, authored the study, which was published Wednesday, Sept.18 in the journal Cell Communication and Signaling.

Kotula has long been a leading researcher of the ABI1 adaptor protein, which is found in most cells in the human body. Kotula’s recent research has found that ABI1 may play a significant role in how prostate cancer spreads.

Prostate cancer, which affects more than a million men around the world each year, is the most frequently diagnosed cancer and second most common cause of death in American men.

“Despite the significant advancement in research and medical treatments for early stages of prostate cancer, mortality rates from prostate cancer remain steady with about 30,000 deaths per year. Therefore, understanding the mechanisms underlying metastatic potential of prostate cells is critical,” Kotula and Upstate MD/PhD student Maria A. Ortiz, wrote in a piece to accompany the study.

Their study focused on ABI1, which Kotula believes is a key regulator of the epithelial mesenchymal transition, a process that plays a crucial role in cancer progression. Inactivation of ABI1 and resulting lower concentrations of its associated protein are evident in metastatic prostate cancer cell lines, according to the study. The study found that expression of the ABI1 gene was much lower in tumors than in healthy cells.

“Low ABI1 expression was especially associated with the most aggressive tumors,” according to the study. “The multifunctional ABI1 brings a better understanding of several pathways involved in cancer progression and metastasis. This knowledge allows us to further reduce the complexity surrounding cancer signaling, with hopes to be able to generate more targeted treatments with better patient outcomes.”

Upstate’s chair of urology, Gennady Bratslavsky, MD, helped facilitate a relationship with renowned prostate cancer researcher Martin E. Gleave, CM, MD, FRCSC, FACS, in Canada who provided access to a collection of more than 500 tumors, Kotula said. The sample array included low-grade, non-invasive tumors as well as high-grade, very invasive tumors. The variety was extremely helpful to the research and study, he said.

Kotula said he has been studying the ABI1 gene since 1995. The work that produced the recently published study is supported by a National Institutes of Health grant.

“It’s very exciting as it’s a very big study involving a multidisciplinary approach,” Kotula said. The paper indicates a novel role for the ABI1 gene in tumor progression and brings new ideas to how existing and new drugs could be used to treat prostate cancer.

“The finding of ABI1 mediated regulation of EMT brings the potential for novel use of some already developed drugs, which target this pathway, opening possibilities for better treatment options in metastatic prostate cancer,” Kotula wrote. “These drugs could shrink the tumor size and/or prevent cells from moving to other organs; ultimately they could kill tumor cells.”

Caption: Leszek Kotula, MD, PhD, an associate professor of urology, biochemistry and molecular biology, in his lab at Upstate Medical University.