Quality of life for patients with oral cancer can be dismal, as cancer-related pain is a significant issue for these patients. Nonviral gene delivery method for treating oral cancer pain safely and effectively is being investigated with a $1.2 million, 3-year grant from the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health (NIH).1
“Most of my oral cancer patients have severe pain,” said Brian L. Schmidt, DDS, MD, PhD, professor in the Department of Oral and Maxillofacial Surgery at New York University College of Dentistry (NYU Dentistry) and director, NYU Bluestone Center for Clinical Research and the NYU Oral Cancer Center, New York, New York. “A recent study revealed that oral cancer pain is often more severe than pain from any other type of cancer.”
The severe pain results in difficulty eating, drinking, or talking for patients with oral cancer. This leaves doctors with little or no choice other than to prescribe high doses of opioid medications.
Off-target effects produced by pharmacologic agents that lack anatomical specificity challenge pain treatment in oral cancer, notes Schmidt. “Since high opioid doses generate unwanted side effects that create additional unintended suffering for the patient.”
“Gene therapy is emerging as an exciting alternative to opioids for the treatment of cancer pain,” says Seiichi Yamano, DDS, PhD, DMD, MMSc, associate professor in the Department of Prosthodontics at NYU Dentistry. “We seek to alleviate oral cancer pain by reversing epigenetic changes. Our gene therapy method will set the stage for a new class of medicines that selectively disrupt nociceptive signaling with fewer off-target effects. Our long-term goal is to develop an effective and safe treatment for oral cancer pain.”
Schmidt’s research team demonstrated that OPRM1 (the gene for the μ-opioid receptor) is methylated and down regulated in oral cancer tumors. Furthermore, they demonstrated that OPRM1 re-expression following viral gene transduction significantly reduced cancer pain in a preclinical model. Expression of the μ-opioid receptor on the cancer led to the secretion of opioids into the cancer microenvironment.
Yamano responded to safety concerns and the inefficiency of viral transduction by creating 2 novel nonviral hybrid vectors: a cell-permeable peptide (CPP) combined with either a cationic lipid (CPP/lipid) or a cationic polymer (CPP/polymer). These nonviral vectors have excellent transfection efficiency with little cytotoxicity across a range of cell lines including different types of cancer cells.
“In addition to their transfection efficiency, my nonviral vectors preferentially transfect oral cancer cells compared to normal cells,” said Yamano. “Transfection efficiency using the nonviral vector in oral cancer cells showed 8-fold more gene transfer than normal cells and higher expression than that for an adenoviral vector.”
1. New York University. NYU to investigate gene delivery for the treatment of oral cancer pain [news release]. EurekAlert! website. http://www.eurekalert.org/pub_releases/2016-06/nyu-nti062716.php. Published June 27, 2016. Accessed June 30, 2016.