Oral anti-fungal drug can treat skin cancer in patients

February 4, 2014 by Ranjini Raghunath

(Medical Xpress)—Decades of research and millions of dollars go into developing new cancer drugs from scratch. But what if the next cure is a pill that's already tucked away in a bottle at the local pharmacy?

One such drug, a common anti-fungal treatment called itraconazole, may be useful in treating —the most common form of skin cancer, according to a study that was published online Feb. 3 in the Journal of Clinical Oncology.

The study tested itraconazole's effectiveness in treating patients with multiple basal cell carcinoma tumors. Researchers at the Stanford University School of Medicine carried out a phase-2 clinical trial with 29 patients who had a total of 101 tumors. Within a month, the size and spread of tumors had decreased in most patients, they found.

Basal cell carcinoma affects nearly 3 million people in the United States every year. Triggered mainly by excess sun exposure, it is rarely fatal, but advanced-stage tumors can cause pain and skin disfigurement. Older adults with light skin are particularly at risk.

The study describes the first evidence of itraconazole's usefulness in treating this type of skin cancer. It also demonstrates how an existing drug can be repurposed to treat cancer, said Jean Tang, MD, PhD, associate professor of dermatology and the senior author of the study. Daniel Kim, a graduate student at Stanford, is the lead author.

"New drugs cost about $800 million and an average of 10 years to develop," Tang said. "We are shortcutting the process by using a drug that's already been around for 25 years and given to tens of thousands of people."

Itraconazole, which is prescribed for common fungal infections, kills fungal cells by blocking the production of a vital membrane component. In cancer cells, the drug appears to disable the Hedgehog signaling pathway—a cascade of cellular events triggered by the Hedgehog protein signal that is vital to cell growth and development.

The Hedgehog pathway was first identified for its role in controlling how the fruit fly's body is divided into segments. Fly embryos lacking the pathway's key protein messenger resembled spiny hedgehogs. Proteins in the pathway relay vital signals for cells to grow and divide in embryos and tumors. In healthy adult cells, the pathway is mostly involved in maintaining and repairing tissues. It also plays a role in regulating how stem cells generate different cell types.

Researchers previously showed that mice with improperly activated or absent Hedgehog proteins can develop cancers and deformed vital organs.

For the current study, Tang teamed up with co-author Philip Beachy, PhD, professor of biochemistry and of developmental biology, who has been studying the Hedgehog signaling pathway for many years.

In 1998, Beachy's lab identified the first known inhibitor of the Hedgehog pathway—a plant compound called cyclopamine—as well as several chemical alternatives. But they knew that developing commercial drugs to target the from scratch could be a tedious and financially risky process.

Four years ago, Beachy, along with then-postdoctoral scholar James Kim, MD, PhD, published a study identifying drugs that had already been approved by the Food and Drug Administration, or previously tested in , that could block the Hedgehog pathway. Kim is also a co-author of the current study.

"We realized that if there are drugs already out there with the potential, it would be much easier to bring them to patients," said Beachy, who is also the Ernest and Amelia Gallo Professor in the School of Medicine.

Some of the 2,400 drugs they screened showed potential. But itraconazole was the most promising because it could block the Hedgehog pathway at the normal dosage prescribed for fungal infections. Mice treated with itraconazole showed greatly reduced tumors.

Tang then carried out the first set of clinical trials, and those findings are reported in the new paper. Patients were given itraconazole pills twice a day for a month. Another small group was given a lower dosage of itraconazole for a longer duration (an average of 10 weeks).

In the first group, the drug reduced Hedgehog pathway activity by an average of 65 percent and tumor size by 24 percent. Patients in the second group, with lower itraconazole doses, showed similar reductions in tumor size.

"The next step is to test itraconazole in more patients for a longer time to really measure its anti-tumor effect relative to other treatments," Tang said. Side effects of itraconazole (sold under the brand name Sporanox) are generally mild and include nausea, fatigue and dizziness. In rare cases, it can cause liver dysfunction. Patients with congestive heart failure or a history of heart disease are not advised to take itraconazole.

Tang's previous work focused on clinical trials of vismodegib, the first FDA-approved basal cell carcinoma drug tailored to shut down the Hedgehog pathway. Vismodegib was found to be highly potent and is currently considered the first line of treatment for advanced basal cell carcinoma tumors. But the drug took years to discover and develop, and a yearlong prescription costs patients about $90,000—or roughly $250 a day.

Although itraconazole does not appear as effective as vismodegib on advanced tumors, it may potentially treat smaller tumors and is much less expensive, costing about $20 a day.

"An interesting feature of itraconazole is that it can inhibit cancer cells that have developed resistance to vismodegib or other cancer drugs that block the Hedgehog pathway," Beachy said. "It may work better as an alternative treatment or in combination with other treatment options."

Tang is now working on clinical trials testing a combination of and arsenic trioxide in patients resistant to vismodegib treatment.

Explore further: Studies show new drug to be effective in treating skin cancer

More information: "Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma." Daniel J. Kim, James Kim, Katrina Spaunhurst, Javier Montoya, Rita Khodosh, Kalyani Chandra, Teresa Fu, Anita Gilliam, Monserrat Molgo, Philip A. Beachy, and Jean Y. Tang. JCO, published online on February 3, 2014; DOI: 10.1200/JCO.2013.49.9525

Related Stories

Studies show new drug to be effective in treating skin cancer

June 6, 2012
A new drug has been shown to be effective in treating and preventing the most common cancer in the United States: basal cell carcinoma skin cancer, according to a new study in the New England Journal of Medicine to be published ...

New study opens door to multipronged attack against skin common cancer

February 27, 2013
Hailed as a major step forward in the effort to develop targeted cancer therapies, a recently approved drug for the most common type of skin cancer has been a mixed blessing for patients. Although the initial response is ...

Antifungal drug delays need for chemo in advanced prostate cancer

June 2, 2011
The oral antifungal drug itraconazole, most commonly used to treat nail fungus, may keep prostate cancer from worsening and delay the need for chemotherapy in men with advanced disease. Details of the finding, from a clinical ...

Chemo may get boost from cholesterol-related drug

April 3, 2012
Johns Hopkins investigators are testing a way to use drugs that target a cholesterol pathway to enhance the cancer-killing potential of standard chemotherapy drugs. Their tests, in mouse models of pancreatic cancer, may yield ...

Recommended for you

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

Searching for the 'signature' causes of BRCAness in breast cancer

August 21, 2017
Breast cancer cells with defects in the DNA damage repair-genes BRCA1 and BRCA2 have a mutational signature (a pattern of base swaps—e.g., Ts for Gs, Cs for As—throughout a genome) known in cancer genomics as "Signature ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.