Recently, a team of Yale researchers led by Dr. Murat Gunel, Nixdorff-German Professor of Neurosurgery and Professor of Genetics and Neurobiology, was able to diagnose an 18-month-old girl from Turkey with a rare form of liver cancer using breakthrough genetic technology. By mapping out her individual genetic sequence, Gunel proceeded to develop a personalized cure.
When she was eight months old, Derin began to show strange signs of discomfort and a lack of desire to eat, drink, and sleep. Worried by these severe and persistent symptoms, her parents immediately looked to the medical community for answers. It took Turkish doctors ten months to discover the source of Derin’s illness, a tumor in her liver. This tumor, however, turned out to be a rare form of liver cancer with only ten known reported cases, leaving the doctors perplexed and uncertain about how to treat it. They proposed performing a liver transplant, a stressful and dangerous procedure for a toddler to undergo.
Seeking further and immediate medical attention, Derin’s parents brought her to the Yale-New Haven Children’s Hospital, where Gunel and his colleagues rapidly diagnosed her and set to work on developing a cure. Unlike most standardized cancer treatments such as surgery, chemotherapy, and radiation, where all patients receive the same methods and therapies, Gunel turned to a personalized approach to treat Derin’s rare cancer.
Gunel extracted a 1-mm by 3-mm slice of Derin’s parenchymal tissue from her liver and used it to map out her genetic code. In only five days, doctors found a mutation in the DNA sequence that encodes for a protein responsible for bile salt secretion. Bile salts are synthesized in the liver from cholesterol and help remove lipids from the body. Derin’s mutation led to these bile salts accumulating in her liver, creating a harmful build-up that led to her cancer.
Professor David F. Stern, Professor of Pathology at the Yale School of Medicine and a member of the Yale Cancer Center who was not affiliated with Gunel’s research, elaborated on the process of identifying the mutations. “Dr. Gunel’s approach was to sequence the tumor cell DNA and compare it to the DNA found on a normal, healthy liver cell,” said Stern. “Researchers detected a number of differences, focused on the ones that were known to have an impact in causing cancer, and found the mutation in the ion channel involved in bile salt secretion. This mutation had possibly already been connected to cancer in some way.”
In a series of life-saving steps, the surgeons at the Yale-New Haven Children’s Hospital removed the tumor without harming the liver by using her genomic data to identify malignant cell types. They then created an exit pathway for the bile salt build-up, ensuring that it would have no long-term consequences for Derin’s health. Derin was monitored in case her cancer spread beyond the liver, but in the meantime, her family was reassured that Derin was healthy and could go home soon.
Derin’s treatment represents the beginning of a new approach to fighting, and winning, the battle against cancer. In the past, scientists have looked at cancers as diseases that attack each individual in the same way. Now, researchers and surgeons are beginning to detect the exact locations in the genome of each patient where carcinogenic agents induce mutations, such as single nucleotide substitutions or DNA damage, that can lead to tumor formation.
Genetic mapping provides a useful tool in diagnosing other cancers as well. “Some cancers, such as those of the lung, experience mutations in mostly the same areas, so there are already specific drugs that can bind to the genes or their protein products and help regulate them in all patients,” said Stern. “Yet, there is an overwhelming number of mutations for which no drugs exist yet that can help.” However, catalogues that contain tumor classifications through genetic screening are becoming more commonplace. Based on these genetic screens, drugs used to treat certain types of cancer could be repurposed to treat other kinds as well.
Dr. Gunel’s work not only paves the way for further advances in the field of cancer research, but also adds to the growing practice of using personalized medicine as a more effective way of treating patients. This focus on basing treatments on individual needs may be the next step forward in cancer therapy.
Cover Image: Close up of parenchymal tissue extracted from liver. Image courtesy of WTNH.