Molecular chain of events identified in prostate and lung cancer progression

Paul Basilio, MDLinx | May 10, 2017

Researchers at the University of Pennsylvania have identified a new molecular chain of events in a mouse model of prostate cancer that may highlight novel treatment targets for multiple cancers, according to a study published in Cell Reports.

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Penn researchers are trying to identify compounds to block CXCR5 or CXCL13 and study their potential as anti-cancer agents.

The team, led by Marcelo Kazanietz, PhD, Professor of Systems Pharmacology and Translational Therapeutics at Penn Medicine, reported that the overexpression of the protein PKCε with the loss of the tumor suppressor Pten causes the progression of prostate cancer.

The combination of these events causes an uptick in the levels CXCL13, a cancer-promoting molecule. During the study, the team disrupted CXCL13 or CXCR5—the cell-surface receptor to which it attaches—and found that the metastatic and tumor-forming characteristics of the mouse prostate cancer cells were impaired.

“In addition to providing evidence for a vicious cancer cycle driven by PKCε, our studies identified a compelling rationale for blocking the CXCL13-CXCR5 molecules as a new cancer treatment,” Dr. Kazanietz said.

He and colleagues plan to identify compounds to block CXCR5 or CXCL13 and to study their potential as anti-cancer agents. The researchers also suggested that CXCL13 levels in blood could be used as a biomarker to measure the precise state of prostate cancer progression in a patient.

In the past, pulmonologists and oncologists have observed the overexpression of PKCε in patients with lung cancer, but the exact molecular consequences were not understood. High levels of PKCε are generally associated with poor prognosis.

“We are in the midst of extending these findings to lung cancer,” Dr. Kazanietz added.

He is currently collaborating with Penn Medicine researchers David Feldser, PhD, Assistant Professor of Cancer Biology, Steven M. Albelda, MD, Professor of Pulmonary, Allergy and Critical Care, and Evgeniy Eruslanov, PhD, a Research Assistant Professor of Thoracic Surgery.

The study was funded in part by the NIH and the Department of Defense.

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