Researchers from Washington University in St. Louis have developed a method for predicting oral cancer’s future aggressiveness, a new study reports, possibly paving the way for better diagnostic tools to guide treatment plans.
Unlike skin cancer, which generally offers clinicians easy and instant observation of any and all tumors, cancers that are embedded in the body’s tissues don’t always show up as clearly on scanners. Taking an alternate route, they rely on blood tests. Specifically, they look for particular gene expressions — patterns reflected in a person’s DNA that reveal predispositions according to what science already knows. The latest study compared mouse genes with those found in human subjects.
"We didn't automatically assume this mouse model would be relevant to human oral cancer," said Dr. Ravindra Uppaluri, associate professor of otolaryngology and co-researcher, in a statement. “But it turns out to be highly reflective of the disease in people."
Uppaluri and his colleagues collected data on 324 human patients to compare them with prior studies showing mouse models expressing certain genes in the presence of head and neck cancers. The research sought to answer a vital and vexing question for Uppaluri, namely, if “all patients with advanced head and neck cancer get similar treatments,” as he says, then why do some meet poor outcomes while others flourish?
The team induced the same tumors found in many heavy tobacco users in mice, using a known carcinogen that tends to yield similar effects. What they found after sequencing the tumors was that key signatures found in both the mice and the human subjects turned out to be nearly identical. Many of the mutations remained constant, with some 120 genes finding commonality between the two groups. Following up on the findings, the team used oral cancer samples from patients treated at the University to develop a proof-of-concept test that would identify the aggressive tumors. It achieved 93 percent accuracy.
Oral cancers are surprisingly common in the U.S., and, given the difficulty in finding and treating tumors, lead to death just over half the time within five years. According to the Centers for Disease Control and Prevention, each year more than 30,000 new cancers of the oral cavity and pharynx emerge. Unfortunately, many cancer patients wear their treatments as scars or physical disfigurement. Avoiding treatment is generally preferable, prompting scientists to uncover new avenues for prevention. Molecular targets, like the ones pursued in Uppaluri’s lab, are the latest.
"These kinds of tests are available for other types of cancer, most notably breast cancer," he said. "They are transformative genetic tests that can alter the clinical management of patients, tailoring therapies especially for them. It's our goal to develop something like that for head and neck cancer."
Source: Onken M, Winkler A, Kanchi K, et al. A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease. Clinical Cancer Research. 2014.