Worldwide, head and neck cancer is the sixth-most common form of cancer worldwide; in addition, it accounts for 5% of cancers diagnosed annually in the United States. Of the more than 42,000 individuals diagnosed with head and neck cancer each year, 12,000 will die from the disease. Researchers at UCLA’s Jonsson Comprehensive Cancer Center have discovered that a protein that may improve the effectiveness of chemotherapy treatments for these cancers. The study was published online on October 20 in the Journal of Biological Chemistry.
The protein discovered by the researchers is commonly associated with rare neurological disorders but is also associated with head and neck cancer in people who are infected with the human papillomavirus (HPV). When the protein is combined with another cancer-suppressing protein, it benefits chemotherapy. HPV is the most common sexually transmitted disease (STD), and HPV diagnoses are currently at epidemic proportions. The Centers for Disease Control and Prevention (CDC) estimates that almost all sexually active men and women will become infected during their lifetime.
A research team headed by Eri Srivatsan, PhD and Marilene Wang, MD discovered the link between the protein gigaxonin and head and neck cancer while investigating the chemotherapy drug cisplatin. The drug is successfully able to kill cancer cells by interacting with the protein p16, which is commonly produced in HPV-positive cancers. “We studied the interaction of p16 in the nucleus of the cancer cell after treatment with cisplatin, and observed how the protein interacted with gigaxonin,” explained Dr. Wang, professor-in-residence of head and neck surgery. She added, “We found the combination of the proteins stops the cell cycle, allowing chemotherapy treatment to prevent the cell from growing and killing the cancer cell.”
For the study, the investigators also analyzed 103 archival clinical samples from head and neck cancer patients in order to identify the relationship between p16 nuclear expression and cancer-free survival. They found that patients with cancers with p16 expression had superior survival rates than without p16 expression. HPV is most often related to cervical cancer; however, during the past several years there has been an increase in HPV-positive head and neck cancers, which often affect non-smoking younger adults; in the past, these individuals were not considered to be at high risk for head and neck cancer.
The researchers are hopeful that their new findings will lead to an enhanced form of personalized, targeted therapy for head and neck cancer patients. They hope that it will ultimately lead to a reduction of the severe side-effects of chemotherapy and radiation. “This discovery opens new possibilities in the diagnosis and treatment of HPV-positive head and neck cancers,” explained Dr. Srivatsan.