ddn Cancer Research News exclusive: ‘Cream’ of the cancer treatment crop

RMIT researchers posit potential skin-cancer cream treatment with melanoma- killing peptide

Kelsey Kaustinen
MELBOURNE, Australia—Some of the latest research to come outof the 'land down under' could have far-reaching effects for cancer sufferersall over the globe.
Recent work by a team at RMIT University, has led to thesynthesis of a peptide that mimics the activity of the myxoma virus, acancer-killing virus that demonstrated toxic effects against melanoma inprevious studies. Laboratory tests have shown that the peptide kills melanomacells while leaving healthy skin cells unharmed.
The team, consisting of researchers from RMIT's HealthInnovations Research Institute and the School of Applied Sciences, was led byDr. Taghrid Istivan, lead investigator of the study. The researchers workedwith a peptide, a short chain of amino acids, which was designed to functionlike the proteins of the myxoma virus.
"A virus protein is big, expensive to synthesize and hasinherent risks when used in medical treatments, because all viruses canmutate," said Istivan in a press release. "By synthesizing a small peptide that mimics the actionof a protein, we can offer a stable, safe, targeted and cost-effective alternative." 
The peptide was designed by using a novel bioengineeringmethod developed at RMIT by Prof. Irena Cosic and Dr. Elena Pirogova, from theuniversity's School of Electrical and Computer Engineering, known as theresonant recognition model (RRM). The team synthesized the peptide as a powder,liquefied it and tested it in vitro onnormal human skin cells and melanoma cells.
Istivan notes that the RRM method was "put into very limitedapplications until 2008 when we teamed together in an attempt to put this modelinto application to design and test RRM designed anticancer therapeuticpeptides." To begin with, Pirogova designed "bioactive peptides as analoguesfor known therapeutic proteins like TNF alpha, interleukin 12 and we alsoincluded an analogue for myxoma virus proteins," says Istivan. A representativewas chosen from each group to be commercially synthesized and tested along witha negative control peptide, she explains, adding that the results from thefirst experiment were "great."
"I did not believe my eyes when I looked under themicroscope to see the treated mouse melanoma cell cultures dead even with verylow concentrations of each of the bioactive peptides, while there was no effectat all by the negative control peptide and the non-treated cells," saysIstivan. "We were more encouraged when we tested these peptides on normal mousecells (fibroblasts and macrophages) and did not see any toxic effect on thesecells too. Since then, we have performed in vitro tests on human melanoma and human skin carcinoma cell cultures, andthe results were very positive as before. We also tested normal human cellsincluding dermocytes, fibrocytes and human red blood cells, and there was noeffect on any of these normal cells."
Istivan notes that they are unsure as to how exactly thepeptide is able to target melanoma cells without harming surrounding healthycells, but they do know "that these peptides are targeting specific sugarspresented on membranes of melanoma cells, and it is known that cancer cellsexpress different glycomic groups from those of normal cells." The team isinvestigating molecular targets for the peptides in cancer cells, she adds, inorder to determine the mechanism of action. While the peptide has proven to beeffective in different types of skin cancers in vitro, it has not yet been tested whether it is effectivein both early and late stages of melanoma.
In the United States alone, the American Cancer Societypredicts approximately 76,250 new cases of melanoma in 2012, as well as 9,180deaths. The World Health Organization notes that "132,000 melanoma skin cancersoccur globally each year." Many of those cases occur in Australia, wheremelanoma is known as the country's "national cancer." According to Istivan,Australia has the highest incidence of melanoma worldwide, seeing "more than11,000 new diagnoses each year," with melanoma accounting for a staggering 75percent of skin cancer deaths in the country.

The current standard of care for melanoma consists ofsurgery, followed by chemotherapy, radiation or immunotherapy if remissionoccurs. If melanoma is found early, chances are good for treatment throughsurgery, Istivan explains, with chances of remission or metastasis depending onhow deeply the cancer has spread into the epidermis. Ideally, however, theresearchers hope that "our research could lead to the development of a cream topainlessly and efficiently treat early-stage melanoma," she says.
Istivan says that this approach could have potential intreating other types of cancer as well, noting that "we have tested the effectof one of the peptides on a human prostate cancer cell line, and it is veryeffective."
Moving forward, Istivan and her colleagues will be testingthe peptides in laboratory animals, and then, "depending on availability ofresearch funding and based on the results of animal experiments, we aim toproceed to clinical trials for the anticancer cream." They will also seek toexpand their testing into other types of cancer, primarily breast and prostatecancer, and "to understand the mode of action in each type of cancers." Animalexperiments are planned for early 2013.

Kelsey Kaustinen

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