BreakThrough Digest Medical News

Fox Chase researchers show that a promising drug can help prevent head and neck cancers

Posted: 08 Apr 2013 09:00 PM PDT

Head and neck cancers typically begin in squamous cells that line moist surfaces inside the mouth, nose and throat. Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common type of cancer in the United States, and it is sometimes preceded by the appearance of changes inside the oral cavity called precancerous lesions. The most common type of change is a white patch known as a leukoplakia. Because it often takes decades for leukoplakias to develop into HNSCC, there is a window of opportunity to recognize and revert precancerous changes, thus preventing this type of cancer.

Researchers at Fox Chase Cancer Center have brought the field one step closer to the goal of prevention by demonstrating the efficacy of a promising naturally occurring agent that targets a gene that is important for the growth of leukoplakia cells in the mouth. They will present the findings at the AACR Annual Meeting 2013 on Tuesday, April 9.

They found that pharmacological inhibition of this gene, called cytochrome P450 1B1 (CYP1B1), led to a decrease in the movement and proliferation of leukoplakia cells. This research, was carried out by Ekaterina G. Shatalova, PhD, Research Associate at Fox Chase, and Margie L. Clapper, PhD, Co-leader of the Cancer Prevention and Control Program at Fox Chase.

“The difficulty in treating head and neck cancer is that the majority of the patients are diagnosed at advanced stages. This is one of the reasons why the five-year survival rate for head and neck cancer is only 40 to 50 percent,” says Dr. Shatalova. “So the earlier we can treat these patients, the better.”

The CYP1B1 protein metabolizes tobacco smoke and ethanol, known risk factors for head and neck cancer, generating potentially carcinogenic compounds. Shatalova, Clapper and their colleagues previously found that genetic deletion of CYP1B1 dramatically reduced the migration and proliferation of leukoplakia cells taken from the mouths of patients. “In the present study, we wanted to see if treating the same cells with a pharmacologic CYP1B1 inhibitor, which could possibly be used in humans, would have the same effect on cell motility and proliferation as genetic manipulation,” Shatalova says.

In the new study, the researchers used homoeriodictyol (HED), a common dietary flavonoid that selectively inhibits CYP1B1. Consistent with their previous findings, exposure of leukoplakia cells to HED for several days resulted in an approximate seven-fold decrease in the rate of cell movement, as well as a 33 percent decrease in proliferation, when compared with untreated cells.

“Because the compound we used is abundant in citrus fruits and it is considered by the Food and Drug Administration to be a safe food additive, it is likely to be non-toxic to humans and thus could represent a promising agent for routine use,” Shatalova says.

Moving forward, the researchers will test whether HED treatment reduces tumor growth and metastasis in animal models. “These novel effects of CYP1B1 inhibition could guide efforts to establish new strategies for the prevention and treatment of head and neck cancers,” Shatalova says.

###

Fox Chase Cancer Center, part of Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase also was among the first institutions to receive the National Cancer Institute’s prestigious comprehensive cancer center designation in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are routinely recognized in national rankings, and the Center’s nursing program has achieved Magnet status for excellence three consecutive times. Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research and oversees programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE (1-888-369-2427) or visit http://www.foxchase.org.

Contact: Diana Quattrone
diana.quattrone@fccc.edu
215-728-7784
Fox Chase Cancer Center

New treatment holds promise for resistant lung cancer

Posted: 08 Apr 2013 09:00 PM PDT

A new chemotherapy regimen appears to produce minimal side effects in patients with lung cancer that has not responded to previous therapy, paving the way for additional research to determine if the new regimen also helps shrink tumors, according findings to be presented by Fox Chase Cancer Center researchers at the AACR Annual Meeting 2013 on Tuesday, April 9.

“I’m very optimistic that we will show this protocol helps lung cancer patients who have run out of other options,” says study author Hossein Borghaei, MS, DO, director of Thoracic Medical Oncology at Fox Chase. “For this patient population, we are in desperate need of new treatments.”

All of the patients included in the study had non-small cell lung cancer, the most common form of lung cancer. In the U.S., more patients die of lung cancer than any other cancer. All had tried at least one other treatment, but their tumors had continued to grow.

Once patients fail to respond to one therapy, additional treatments are less likely to work, says Borghaei. For patients with treatment-resistant lung cancer, there is often little hope. But in the labs of Fox Chase, researchers have found evidence that a new combination of existing chemotherapy drugs could have an effect on these types of tumors.

The first drug, Tarceva (erlotinib), blocks a pathway many tumors use to grow. The drug works particularly well in lung tumors that carry a mutation which accelerates that particular pathway. None of the patients included in the study carried this mutation, but research suggests they may still see some benefit from Tarceva.

The other drug, Alisertib (MLN8237), prevents chromosomes from splitting normally during cell division, causing cells to die. Since tumors depend on cell division to grow, the drug is being investigated in a number of different types of cancer.

If the drugs work better together than apart in lung tumors, that would make sense, says Borghaei. “What we’ve found through many years of research is that it’s often better to combine chemotherapy drugs that target different aspects of cancer than to use either alone.”

To test this theory, Borghaei and his colleagues gave four different doses of the drugs to 10 patients?the first stage of clinical testing that determines the maximum dose that people can safely tolerate.

Encouragingly, the side effects were “manageable,” says Borghaei. One person experienced hair loss and lower counts of blood cells that fight infection, but has not developed any infections, he says. Other patients reported some mild fatigue, “but nothing out of the ordinary that would make us say this is an intolerable regimen,” he says.

Although the research is not far enough along to know if the treatment works, 2 patients’ tumors stopped growing while taking the drugs. Three patients have unfortunately died, but only after they’d stopped the treatment because their tumors didn’t respond.

Borghaei cautions that in such early stages of the research, it’s too soon to tell if the treatment works. “Both patients whose tumors stabilized were given the maximum dose of both drugs, and I hope that once we progress in the trial and treat more patients at the maximum doses, we will see more responses,” he says. “I want everyone to respond.”

###

Co-authors on the study are Ranee Mehra, Sam Litwin and Igor Astsaturov from Fox Chase.

Contact: Diana Quattrone
diana.quattrone@fccc.edu
215-728-7784
Fox Chase Cancer Center