Much like a criminal profiler tracking a suspect, a Carle Illinois College of Medicine researcher is tracking lipids in her quest to discover new tools for diagnosing and treating cancers that start in the head and neck. The research uses two powerful tools – mass spectrometry and bioinformatic data from patients with these cancers – to identify and profile lipid biomarkers that could flag head and neck cancers through routine blood tests.
CI MED Research Associate Professor Chitra Subramanian, who is also director of the Translational Oncology and Regenerative Medicine (TORM) Laboratory, has set out to discover how the growth and metabolism of fatty, waxy lipids in the blood contribute to cancers in the head, neck, and adrenal glands. “Lipids play an important role in tumor development and the progression of cancer and can be very specifically overproduced in several tumors, including head and neck cancer,” Subramanian explained.
Her team’s prime target is both diagnosis and treatment for squamous cell carcinoma of the head and neck (HNSCC), an aggressive cancer that attacks cells in the oral cavity, throat, lip, nasal cavity, sinuses, and salivary glands. Currently, the prognosis for advanced HNSCC is poor and there are no routine screening protocols in place for early diagnosis.
Using an analysis method known as mass spectrometry, Subramanian’s team compared the lipid signatures found in the tumors of 63 head and neck cancer patients with the lipids found in nearby healthy tissue. The researchers found significant differences in the regulation of two major types of lipids – phospholipids versus glycerolipids, which include triglycerides. With these clues, Subramanian’s team is identifying specific biomarkers that could make diagnosis possible through simple blood tests. “Since most individuals undergo routine blood tests, identifying these biomarkers can enable early detection of HNSCC,” Subramanian said, adding that the team’s method could pinpoint personalized biomarkers that allow for improved monitoring for patients already diagnosed with HNSCC.
Subramanian also believes lipid metabolic profiling of HNSCC holds unique, untapped potential to identify new treatments. “We found that blocking the activity of a specific enzyme [Phospholipase A2, PLA2] using a signaling pathway [AKT pathway] resulted in significant growth reduction of HNSCC xenograft [tumor samples tested in animal models] without any measured toxicity. This is a very exciting, novel, and highly translatable treatment option for squamous cell carcinoma of the head and neck,” Subramanian said.
Subramanian is also the lead investigator of a CI MED team that received a $200,000 grant from the Cancer Center at Illinois to study ironmetabolism in these cancers. Cancer Center at Illinois program leader Zeynep Madak Erdogan is the project co-leader, and CI MED Dean Dr. Mark Cohen is a co-investigator in that study.
Subramanian’s research lab seeks to find ways to repurpose drugs that are already approved for other therapeutic uses to treat forms of cancer, including adrenal cancer and neuroblastoma (a rare pediatric cancer). “As a result of our research, we have found that several drugs, such as SurVaxM (used for treating glioblastoma), Fingolimod (used for treating multiple sclerosis), and sulfasalazine (used for inflammatory bowel disease and arthritis), can be repurposed for treating adrenal cancer. We have proved the efficacy of these drugs in vitro and plan to conduct in vivo [i.e., within a living organism] research for further clinical translation,” Subramanian said.
Editor’s note: In addition to her role at CI MED, Professor Subramanian is affiliated with the Cancer Center at Illinois and the Beckman Institute at the University of Illinois Urbana-Champaign.