ddn Cancer Research News exclusive: ‘Cream’ of the cancer treatment crop
MELBOURNE, Australia—Some of the latest research to come out of the 'land down under' could have far-reaching effects for cancer sufferers all over the globe.
Recent work by a team at RMIT University, has led to the synthesis of a peptide that mimics the activity of the myxoma virus, a cancer-killing virus that demonstrated toxic effects against melanoma in previous studies. Laboratory tests have shown that the peptide kills melanoma cells while leaving healthy skin cells unharmed.
The team, consisting of researchers from RMIT's Health Innovations Research Institute and the School of Applied Sciences, was led by Dr. Taghrid Istivan, lead investigator of the study. The researchers worked with a peptide, a short chain of amino acids, which was designed to function like the proteins of the myxoma virus.
"A virus protein is big, expensive to synthesize and has inherent risks when used in medical treatments, because all viruses can mutate," said Istivan in a press release. "By synthesizing a small peptide that mimics the action of a protein, we can offer a stable, safe, targeted and cost-effective alternative."
The peptide was designed by using a novel bioengineering method developed at RMIT by Prof. Irena Cosic and Dr. Elena Pirogova, from the university's School of Electrical and Computer Engineering, known as the resonant recognition model (RRM). The team synthesized the peptide as a powder, liquefied it and tested it in vitro on normal human skin cells and melanoma cells.
Istivan notes that the RRM method was "put into very limited applications until 2008 when we teamed together in an attempt to put this model into application to design and test RRM designed anticancer therapeutic peptides." To begin with, Pirogova designed "bioactive peptides as analogues for known therapeutic proteins like TNF alpha, interleukin 12 and we also included an analogue for myxoma virus proteins," says Istivan. A representative was chosen from each group to be commercially synthesized and tested along with a negative control peptide, she explains, adding that the results from the first experiment were "great."
"I did not believe my eyes when I looked under the microscope to see the treated mouse melanoma cell cultures dead even with very low concentrations of each of the bioactive peptides, while there was no effect at all by the negative control peptide and the non-treated cells," says Istivan. "We were more encouraged when we tested these peptides on normal mouse cells (fibroblasts and macrophages) and did not see any toxic effect on these cells too. Since then, we have performed in vitro tests on human melanoma and human skin carcinoma cell cultures, and the results were very positive as before. We also tested normal human cells including dermocytes, fibrocytes and human red blood cells, and there was no effect on any of these normal cells."
Istivan notes that they are unsure as to how exactly the peptide is able to target melanoma cells without harming surrounding healthy cells, but they do know "that these peptides are targeting specific sugars presented on membranes of melanoma cells, and it is known that cancer cells express different glycomic groups from those of normal cells." The team is investigating molecular targets for the peptides in cancer cells, she adds, in order to determine the mechanism of action. While the peptide has proven to be effective in different types of skin cancers in vitro, it has not yet been tested whether it is effective in both early and late stages of melanoma.
In the United States alone, the American Cancer Society predicts approximately 76,250 new cases of melanoma in 2012, as well as 9,180 deaths. The World Health Organization notes that "132,000 melanoma skin cancers occur globally each year." Many of those cases occur in Australia, where melanoma is known as the country's "national cancer." According to Istivan, Australia has the highest incidence of melanoma worldwide, seeing "more than 11,000 new diagnoses each year," with melanoma accounting for a staggering 75 percent of skin cancer deaths in the country.
The current standard of care for melanoma consists of surgery, followed by chemotherapy, radiation or immunotherapy if remission occurs. If melanoma is found early, chances are good for treatment through surgery, Istivan explains, with chances of remission or metastasis depending on how deeply the cancer has spread into the epidermis. Ideally, however, the researchers hope that "our research could lead to the development of a cream to painlessly and efficiently treat early-stage melanoma," she says.
Istivan says that this approach could have potential in treating other types of cancer as well, noting that "we have tested the effect of one of the peptides on a human prostate cancer cell line, and it is very effective."
Moving forward, Istivan and her colleagues will be testing the peptides in laboratory animals, and then, "depending on availability of research funding and based on the results of animal experiments, we aim to proceed to clinical trials for the anticancer cream." They will also seek to expand their testing into other types of cancer, primarily breast and prostate cancer, and "to understand the mode of action in each type of cancers." Animal experiments are planned for early 2013.