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Orientation MC1R in metastatic melanoma

November 27, 2018 8:36

In 1960, scientists described the "Philadelphia chromosome", which causes chronic myeloid leukemia,and in 2001 for the control of the Food and Drug Administration approved the drug imatinib to disable the effect of genetically modified cancer. It was the dawn of genetically targeted therapies against cancer, and it seemed that many types of cancer will fall into a similar strategy: find a genetic difference between cancer cells and healthy cells and then develop drugs aimed at the difference. Of course, it was rarely that simple. It is difficult to find a genetic difference that is common to all cells within the same cancer, and many of these differences, it is impossible to target existing drugs strategy. This often seemingly simple gene / drug does not work.

Again, sometimes the drug is effective.

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Research Center of the University of Colorado, published in the journal Science Translational Medicine, describes the genetic variation common to 80 percent of melanomas person, the most deadly form of skin cancer, as well as describes a molecule that looks for cells marked with this genetic variation. In this study, the radiolabel is attached to a target molecule and used positron emission tomography (PET), to show that radioactively labeled molecule actually looks for and binds to melanoma cells. Using this approach, it may be possible not only to see these cells, but also apply to the treatment of this molecule to kill the melanoma cells.

The work begins with a protein called melanocortin-1 receptor (MC1R), which is involved in determining the color of skin and hair, but which is also at a higher level on the surface of more than 80 percent of melanomas person. The present study describes a "peptide" which specifically binds to MC1R. If MC1R is locked, the peptide 68Ga-DOTA-GGNle-CycMSHhex is the key that fits it. In this case, researchers have attached to this peptide radionuclide imaging - a combination of peptide and radionuclide detected related and "lit" metastatic melanoma, allowing researchers to simulate these melanoma cells.

The success of this method of molecular targeting involves the use of a peptide as a carrier for delivery of a therapeutic radionuclide directly in melanoma cells marked MC1R for therapy.

"We attach an imaging radionuclide to the peptide, while the radiolabeled peptide is MC1Rs on melanoma through the blood circulation, allowing us to use the PET machine for collecting signals from the labeled radiolabeled peptide for imaging melanoma. This is a very sensitive method," - said Yubin Miao, PhD, CU Cancer Center investigator and director of radiopharmaceutical science in radiology CU School of Medicine.

In addition, the researchers were able to replace the radioactive label fluorescence to create a new reference sample to determine the fluorescence MC1R (called Cy5.5-GGNle-CycMSHhex). Current research shows that the fluorescent probe binds to and stains the MC1R on melanoma cells. Miao sees that the combination of these two approaches - one radiolabelled and fluorescent one - could potentially improve surgical outcome for melanoma by operation with visualization.

He also sees potential to use a similar strategy as personalized therapeutic approach for patients with metastases in melanoma.

"Approximately 60 percent of patients with metastatic melanoma develop brain metastases during their illness. Patients with brain metastases have a much lower life expectancy than those without metastasis to the brain. Our research shows that the MC1R continues to mark melanoma cells even after the cells metastasize from its origin to the brain, and this peptide can bind to MC1Rs in metastatic melanoma. One of the potential applications of this technology is the use of our imaging systems for identification of MC1R-positive tumors, melanoma, and then treatment of these lesions therapy produced by this peptide - said Miao.

Currently, this study demonstrates the ability to produce the first human melanoma metastases using radiolabeled peptide. Due to the increased funding and cooperation Myao group hopes to explore the therapeutic potential of the treatment in the near future.



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