Studies focus on biomarkers to help guide treatment decisions

March 25, 2016

Two studies by Providence Cancer Center researchers hold the potential to improve therapeutic decision-making in the future. The studies aim to identify biomarkers that may predict a patient's response to immunotherapy, or indicate tumor presence after initial treatment.

“Next-generation immunoprofile”

Researchers at Providence Cancer Center received a $75,000 grant to study biomarkers that may help predict responses to immuntherapy and assist oncologists in making treatment-related decisions for patients with head and neck cancers. The Oral and Maxillofacial Surgery Foundation awarded the grant to Bernard Fox, Ph.D., chief of the Laboratory of Molecular and Tumor Immunology at Providence Cancer Center, and Bryan Bell, M.D., DDS, FACS, director of the Providence Oral, Head and Neck Cancer Program and Clinic, to develop a “next-generation immunoprofile” to help direct therapy for head and neck cancers.

In prior studies, antibodies that target T cell surface proteins, such as anti-PD-1, have produced complete and partial responses as well as durable stable disease in patients with cancer. Despite these successes, it is becoming apparent that for many diseases, only a fraction of treated patients respond to immunotherapy and experience clinical benefit. As a consequence, a major effort is under way to identify biomarkers that can predict clinical efficacy of immune therapeutics to help direct treatment. Providence scientists are using a combination of technologically advanced multi-spectral imaging, objective assessment software, and genetic analysis in their efforts to identify these biomarkers.

“Liquid biopsies”

In a related study, Providence researchers are focusing on developing “liquid biopsies” that can be used to indicate tumor presence after initial treatment for head and neck cancer. Rom Leidner, M.D., co-director of the Providence Oral, Head and Neck Cancer Program, is the principle investigator on the trial sponsored by Resolution Bio, Inc., a next-generation sequencing technology company.

Cell-free circulating tumor DNA (ctDNA) holds the promise to be an excellent quantitative biomarker. In 2007, Vogelstein and Kinzler described a study evaluating ctDNA levels pre- and post-operatively in patients with bowel cancer. In that study, ctDNA levels fell by an average of 99 percent after surgery. In every case where ctDNA was still detectable, patients had disease progression. In cases with undetectable levels of ctDNA, no patients relapsed.

These results suggest that ctDNA may be an effective guide to adjuvant therapy following initial treatment for other cancers, including head and neck cancers, whether treatment is via targeted therapy, immunotherapy, radiation, chemotherapy or surgical resection. Studies have shown that ctDNA has a half-life of less than two hours, effectively making it a real-time indicator of tumor presence. “This technology has the potential to revolutionize how we diagnose and treat cancer,” says Dr. Leidner.