An old antifungal drug will help against skin cancer
A well-known antifungal drug treats skin cancer
NanoNewsNet based on Stanford Medicine: Oral anti-fungal drug can treat skin cancer in patients, study showsThe development of a new anti-cancer drug requires years of research and millions of dollars of financial investments.
But what if the remedy that brings healing to cancer patients is a pill already lying in a bottle on a shelf in the nearest pharmacy?
One such drug, often prescribed for fungal diseases, itraconazole, may benefit in the treatment of basal cell carcinoma, the most common form of skin cancer.
Scientists from the Stanford University School of Medicine conducted phase 2 clinical trials of itraconazole on 29 patients and found that within a month the size and spread of tumors decreased in most patients.
In the USA alone, almost 3 million people get sick with basal cell carcinoma every year. Caused mainly by excessive exposure to the sun, it rarely ends in death, but tumors in the later stages of development cause pain and disfigure the skin.
"The development of a new drug costs about $800 million and requires an average of ten years of work," says the head of the study, associate professor of Dermatology Jean Tang (MD, PhD). "We are shortening the process by using a drug that has been used for about 25 years and prescribed to tens of thousands of people."
Itraconazole, used to treat fungal infections, kills fungal cells by blocking the production of a vital component of the cell membrane. In cancer cells, the drug appears to block the Hedgehog signaling pathway - a cascade of cellular events triggered by the Hedgehog protein signal, which is vital for cell growth and development.
The first established function of the Hedgehog protein was its role in controlling the segmentation of the drosophila fly body. Fly embryos lacking the key protein of this pathway are similar to prickly hedgehogs. Proteins of this pathway transmit vital signals that stimulate the growth and division of embryonic, as well as – alas – and tumor cells. In healthy adult cells, this pathway is mainly involved in maintaining the normal state of tissues and in their restoration. In addition, it plays a role in stem cell differentiation. In mice, abnormal activity or absence of Hedgehog proteins leads to the development of cancer and deformation of vital organs.
In 1998, the laboratory of Professor of Biochemistry and developmental biology Philip Beachy, PhD, who has been studying the Hedgehog signaling pathway for many years, identified the first inhibitor of this pathway – a plant-derived compound cyclopamine (cyclopamine), as well as several of its chemical substitutes. But scientists knew that developing commercial drugs from scratch, the target of which would be the Hedgehog path, is a time–consuming and financially risky process.
Four years ago, Professor Beachy and his colleagues found drugs – already approved by the Food and Drug Administration (FDA) or previously passed clinical trials – capable of blocking the Hedgehog pathway.
"We understood that existing drugs with such potential would be much easier to bring to patients," says Professor Beachy.
Activity blocking the Hedgehog pathway was detected in several of the 2,400 drugs scanned by scientists. But itraconazole seemed to be the most promising, since it worked well in the usual dosage prescribed for fungal infections. In mice treated with itraconazole, there was a significant decrease in the size of tumors.
Dr. Tan then conducted the first series of clinical trials, the results of which are presented in an article published in the Journal of Clinical Oncology (Kim et al., Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma). Patients received tableted itraconazole twice a day for a month. Patients of another small group were prescribed a lower dosage of the drug, but for a longer period (on average 10 weeks).
In the first group, the drug reduced the activity of the Hedgehog pathway by an average of 65 percent, and the size of tumors by 24 percent. In patients of the second group, a similar reduction in the size of tumors was observed.
"The next step will be to test itraconazole on more patients for a longer time to accurately assess its antitumor effect compared to other drugs," says Tan.
The first FDA–approved drug for the treatment of basal cell carcinoma, suppressing the Hedgehog pathway, Vismodegib (Vismodegib) is a highly effective remedy, considered today as a first-line drug for the treatment of late-stage basal cell carcinomas. But it took years to develop it, and the cost of an annual course of treatment is 90 thousand dollars, or about 250 dollars a day.
Although itraconazole is less effective than Vismodegib in the late stages of cancer, it can be used to treat small tumors. It is much cheaper and will cost the patient only $ 20 a day.
"An interesting feature of itraconazole is that it suppresses cancer cells that have developed resistance to Vismodegib or other anti–cancer drugs that block the Hedgehog pathway," says Professor Beachy. "It may be more effective as an alternative treatment or in combination with other treatments."
Portal "Eternal youth" http://vechnayamolodost.ru06.02.2014