Shutting down inflammation within the body, and then harnessing the immune system to recognize and destroy cancer cells, could provide the one-two punch needed to effectively treat head and neck cancers, according to researchers at Icahn School of Medicine at Mount Sinai.
Research into the pivotal role played by the inflammatory molecule inducible nitric oxide synthase (iNOS) in promoting cancer growth and immune evasion is being led by Andrew G. Sikora, MD, PhD, Assistant Professor and Director of Head and Neck Translational Research in the Department of Otolaryngology, Head and Neck Surgery.
This research, and a separate clinical trial for a cancer vaccine that will start in the fall, represent two novel approaches Dr. Sikora’s lab is using to treat patientas with head and neck cancers. There are more than 50,000 new cases in the United States each year, according to the American Society of Clinical Oncology.
According to Dr. Sikora, inhibiting production of nitric oxide (NO) by the iNOS molecule in mouse cancer models alters signal transduction pathways that are critical to the growth and survival of head and neck cancers, including melanoma and squamous cell carcinoma. Combining iNOS therapy with surgery, radiation, or chemotherapy, he says, could produce even more dramatic results.
Most cases of head and neck cancers start in the squamous cells that line the moist, mucosal surfaces inside the mouth, nose, and throat, and are attributed to tobacco and alcohol use, or human papillomavirus infection (HPV).
“First we use iNOS inhibition to sensitize the tumor chemotherapy, cause tumor death, and release antigens that can be recognized by T cells,” says Dr. Sikora. “Then we take the brakes off the antitumor immune response by reversing NO-mediated immune suppression.” The end result would be a robust antitumor immune response capable of destroying residual tumor cells that remain after surgery or radiation therapy.
Dr. Sikora says he is in the process of negotiating with the maker of an iNOS inhibitor drug to move the study from mouse models into clinical trials.
In the separate vaccine study—due to enter Phase 2 clinical trials in the fall—Dr. Sikora and his team will be partnering with Advaxis Inc., a New Jersey based company, to determine whether the bacteria Listeria serves as an effective cancer antigen. After administering the vaccine, Dr. Sikora’s lab will then look for changes in the profile of immune cells in the resected tumors that indicate an effective antitumor immune response.
Says Eric M. Genden, MD, Professor and Chair of the Department of Otolaryngology, Head and Neck Surgery, at Icahn School of Medicine at Mount Sinai: “Dr. Sikora and his team represent Mount Sinai at its best. He is a young, dynamic scientist whose collaborative work is redefining our view of oncology, and elucidating new ways to understand and treat cancers of the head and neck.”