February 10, 2015 | by Darrin Joy
It’s been more than a century since Nobel Laureate Paul Ehrlich popularized the idea of a “magic bullet” targeting disease. Cancer researchers ever since have remained in hot pursuit of targeted therapies that home in on cancer cells while leaving normal cells unaffected.
Linda Malkas, Ph.D., associate chair of the Department of Molecular and Cellular Biology, and her team are making strong headway in that quest. In a study recently published in Molecular Pharmacology, the researchers created a small peptide — a short string of amino acids — that interferes with an altered version of a protein that cancers need to survive.
That protein, called PCNA, normally plays a major role in the process cells use to duplicate their DNA when they divide. It arranges various proteins and enzymes involved with DNA replication so they can do their jobs.
In cancer cells, the part of PCNA that arranges proteins is altered, making it different from normal cells’ PCNA. Malkas’ team created their peptide to mimic the altered region of cancer’s PCNA.
The scientists theorized that the mimic would compete with the cancer’s PCNA, interfering with its function. The tumor cells would then have difficulty replicating their DNA, blocking their ability to multiply. Instead, they would stagnate, eventually shriveling and dying.
In addition, because the peptide mimics cancer’s altered PCNA, it should restrict its activity to tumor cells and have little to no effect on normal cells.
Using treatment-resistant breast cancer cells in the lab, the researchers tested their peptide and found they were right. It did, in fact, prove toxic to the malignant cells while at the same time showing very little toxicity in normal cells, as they hoped.
According to Malkas, who holds the M.T. & B.A. Ahmadinia Professorship in Molecular Oncology, the study is a strong step to bringing this novel therapy to patients.
“Our peptide represents a new and highly targeted therapeutic approach with great potential for a number of cancers,” Malkas said. “The work in this study confirms that we’re on the right track with this peptide mimic.”
The scientists are continuing their studies to better understand the details of how PCNA operates and how the therapeutic effect of the peptide mimic might be boosted.
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