Featured Research

from universities, journals, and other organizations

Researchers design drug to restore cell suicide in HPV-related head and neck cancer

Date:
April 8, 2013
Source:
Ohio State University Medical Center
Summary:
Researchers have discovered a new mechanism by which the human papilloma virus causes head and neck cancer, and they have designed a drug to block that mechanism. The new agent might offer a safer treatment for these tumors when combined with a tapered dose of standard chemotherapy.

Researchers have discovered a new mechanism by which the human papilloma virus (HPV) causes head and neck cancer, and they have designed a drug to block that mechanism. Though further research is needed, the new agent might offer a safer treatment for these tumors when combined with a tapered dose of standard chemotherapy.

HPV-positive head and neck cancer has become three times more common since the 1970s, and it could reach epidemic levels in the future, say researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) who led the study.

"We believe these findings will help meet the real need for more effective and safer therapy for a growing number of HPV-positive head and neck cancer patients," says principal investigator Dr. Quintin Pan, associate professor of otolaryngology at the OSUCCC -- James.

The study was published in the journal Oncogene.

The research, which mainly used head and neck cancer cells, shows that a protein produced by the virus blocks a protein made by the host cell. The cell protein, called p300, regulates a gene called p53. This gene both controls cell division and protects the body against cancer by causing cells to die before they become malignant.

By blocking the cell protein, HPV forces the host cell to live instead of die and to proliferate and form tumors.

The prospective new drug, called CH1iB, prevents the viral protein from binding with the cell protein. This restores the function of the p53 "tumor-suppressor" gene and triggers the death of the cancer cells.

"Our study revealed a new mechanism for p53 inactivation in HPV-positive head and neck cancer, and this allowed us to develop an agent that disrupts that interaction and reactivates p53 in HPV-positive head and neck cancer," Pan says. "Our pre-clinical studies show CH1iB can reactivate p53 and eliminate HPV-positive head and neck cancer cells."

Pan notes that the standard of care for HPV-positive head and neck cancer uses high-dose cis-platinum, a chemotherapy drug that causes serious side effects that are difficult for patients to tolerate. The drug's toxicity raises the need for safer therapy, and, although further testing is necessary, combining CH1iB with a low dose of cis-platinum might one day provide an alternative.

For this study, Pan and his colleagues used high-risk HPV-positive head and neck squamous cell carcinoma cells. Key technical findings include:

  • The small-molecule inhibitor CH1iB inhibits the binding of the HPV E6 protein with the p300 cell protein;
  • The binding of the CH1iB inhibitor with p300 reactivated p53 and dramatically potentiated the efficacy of cis-platinum in HPV-positive head and neck cancer cells;
  • The combination of CH1iB and cis-platinum eliminated 91 percent of HPV16-positive head and neck cancer cells; it also increased apoptosis by 984 percent and 443 percent compared with CH1iB and cis-platinum respectively alone.

"These results suggest that fewer cycles or a tapered dose of cis-platinum, along with a CH1 inhibitor, might be sufficient to effectively manage HPV-positive head and neck cancer patients and offer a better toxicity profile," Pan says.

"Taken together, our data suggest that we've discovered a novel approach for reactivating the p53 gene in HPV-positive head and neck cancer that may translate to other HPV-positive carcinomas."

Funding from the NIH/National Cancer Institute (grant CA135096), the NIH/National Institute for General Medical Sciences (grant GM073943), the Mary E. and John W. Alford Cancer Research Endowment Fund, and a Michelle Theado Memorial Grant from the Joan Bisesi Fund for Head and Neck Oncology Research supported this research.

Other researchers involved in this study were X. Xie, L. Piao, A. Smith, T. Su, M. Zhang and T.N. Teknos of The Ohio State University; and B.N. Bullock and P.S. Arora of New York University.


Story Source:

The above story is based on materials provided by Ohio State University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. X Xie, L Piao, B N Bullock, A Smith, T Su, M Zhang, T N Teknos, P S Arora, Q Pan. Targeting HPV16 E6-p300 interaction reactivates p53 and inhibits the tumorigenicity of HPV-positive head and neck squamous cell carcinoma. Oncogene, 2013; DOI: 10.1038/onc.2013.25

Cite This Page:

Ohio State University Medical Center. "Researchers design drug to restore cell suicide in HPV-related head and neck cancer." ScienceDaily. ScienceDaily, 8 April 2013. <www.sciencedaily.com/releases/2013/04/130408123500.htm>.
Ohio State University Medical Center. (2013, April 8). Researchers design drug to restore cell suicide in HPV-related head and neck cancer. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2013/04/130408123500.htm
Ohio State University Medical Center. "Researchers design drug to restore cell suicide in HPV-related head and neck cancer." ScienceDaily. www.sciencedaily.com/releases/2013/04/130408123500.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins