A drug produced at the N.C. State shows signs of successfully treating lung cancer.
“Sure enough, it appears to work beyond our wildest dreams,” said Ken Adler, professor of cell biology in the College of Veterinary Medicine. “The goal, at some point, is having this drug available as an anti-cancer agent.”
Adler developed the drug peptide while researching the protein myristoylated alanine-rich C-kinase substrate, or MARCKS.
Adler originally became interested in this particular protein almost 15 years ago when he was researching reactive airway disease, a condition similar to asthma.
In diseases of the lung like asthma and chronic bronchitis, sufferers’ airways become inflamed and clog with too much mucus, causing wheezing, coughing and shortness of breath.
The MARCKS protein is found in every cell and has number of different functions. MARCKS plays a role in the normal functioning of cells and the normal production of mucus in the respiratory airways.
Prior to this discovery, there was no way to block the function of the MARCKS protein, Adler said.
Adler discovered that by inhibiting MARCKS protein with a peptide drug, levels of inflammation levels went back to normal.
“It was actually the first means of inhibiting the function of MARCKS protein, and it was used in a variety of different experiments to show different roles of MARCKS and how it’s involved in airway disease,” Adler said.
After the peptide was developed, the technology transfer office at the University went through the process of patenting it and sublicensing it to a biotech company that worked with the University to develop a drug very similar to the original peptide that could be administered to humans.
Following the breakthrough, Adler changed course and began testing the new drug’s ability to block cancer cells from metastasizing.
Adler says what led him to consider the peptide as a treatment for lung cancer was that MARCKS protein controls cell movement.
“The thought was ‘Well, if it blocks cells from moving, what about cancer cells which are known to metastasize?’ meaning cells move from the site of the initial tumor to other parts of the body where they seed and start tumors,” said Adler.
In publishing Adler’s research last week, Oncogene (italicize publication titles), a leading cancer journal, wrote: “These results indicate a crucial role for MARCKS, specifically its phosphorylated form, in potentiating lung cancer cell migration/metastasis.”
Adler did his initial work in collaboration with Reen Wu, a professor of cell biology and human anatomy at the University of California-Davis.
Adler and Wu conducted studies that involved injecting human cancer cells into mice, where tumors and cancer develop in the lung. In numerous experiments they found that not only does the peptide diminish the metastasis of cancer cells, it completely blocks it.
Adler is currently working with a group at the UNC Lineberger Comprehensive Cancer Center to test the peptide on a variety of different types of cancer as well as a variety of models of human cancer.
At the center, cancer in mice is developed through genetic manipulation of the mice rather than injecting them with cancer, as this methodology is closer to what happens when cancer occurs naturally.
It is important to Adler’s research to have the best models of the animals to look at the efficacy and treatment potential of peptides.
Adler said the peptide is a mechanism for controlling cells’ movement as well as cancer cell metastasis, and could therefore potentially be used to treat other cancers.
“My research has always been in lung research … but there is no reason to think that, in the future, it would only be limited to lung cancer,” Adler said. “A lot of the studies we have planned now will involve different types of cancer, including breast cancer, skin cancer, and brain cancer.”