Almost 70 years ago, Dr. Sidney Farber—after whom the Dana-Farber Cancer Institute in Boston is named—created the world’s first chemotherapy drug: methotrexate. Still used today, this drug is powerful yet problematic. As it attacks cancer cells, methotrexate also inflicts significant damage on healthy tissues.
Dr. Naama Kanarek has long been fascinated by the unwanted side effects of cancer therapy. As a doctoral student, she discovered a molecular interaction involved in the onset of mucositis—a painful inflammation associated with cancer radiation treatment. Her findings, published in the prestigious journal Proceedings of the National Academy of Science, may lead to new treatments for radiation-related damage.
As a postdoc, Dr. Kanarek studied the damaging side effects of methotrexate-based chemotherapy. Using the genome editing system known as CRISPR, she discovered why some patients have a stronger reaction to this drug than others.
At the time, it was already known that methotrexate inhibits the production of folate, a B vitamin that helps make and repair DNA, and is also involved in cancer proliferation. But Dr. Kanarek’s research, published in Nature, revealed another influential factor: an enzyme called FTCD.
The job of FTCD is to degrade an amino acid known as histidine. To complete this task, the FTCD enzyme gobbles up folate—the very same metabolite targeted by Dr. Farber’s chemotherapy drug. Dr. Kanarek suspected that, if methotrexate were administered alongside an additional “shot” of histidine, FTCD activity would kick into high gear, reducing folate levels still further—something that would allow chemotherapy to be clinically effective at lower doses. In fact, this is precisely what Dr. Kanarek and her colleagues observed in a mouse model of leukemia, and the implications were huge.
“By creating a ‘cocktail’ comprising both methotrexate and histidine—an amino acid found in almost everything we eat—it may be possible to lower the clinical dosage of methotrexate. This would provide a natural, metabolic strategy for reducing chemotherapy’s damaging side effects,” Dr. Kanarek says.
Her research may also help doctors determine which cancer patients would derive the greatest benefits from methotrexate treatment, and which of them would be non-responders, allowing doctors to steer the latter away from painful and ineffective therapy.
Bio
A native of Jerusalem, Dr. Naama Kanarek trained at the Hebrew University of Jerusalem, where she earned a BSc in medical science (2004), an MSc in proteomics and microbiology (2008), and—in studies that included a year at Columbia University Medical Center in New York—a PhD in immunology and cancer research (2012). Her postdoctoral research (2012–2018) was performed under the supervision of Prof. David Sabatini at MIT’s Whitehead Institute for Biomedical Research.
Dr. Kanarek is the recipient of a number of awards and honors, including the Leukemia and Lymphoma Society New Idea Award (2017), the Hebrew University women in science postdoctoral award (2014), the Weizmann Institute’s Israel National Postdoctoral Award for Advancing Women in Science and a Revson Fellow of that program (2012), and the James Sivartsen Prize in Pediatric Cancer Research (2010). Her postdoctoral work was supported by fellowships from the American Association for Cancer Research (2016) and the European Molecular Biology Organization (2012).
During her postdoc, Dr. Kanarek established No Empty Bedsides (www.noemptybedsides.com), a charitable organization that works in direct partnership with Mass General Hospital for Children to find solutions for parents who, for personal or financial reasons, have difficulty remaining in hospital while their children undergo medical treatment.
Dr. Naama Kanarek is supported by the Charles H. Revson Foundation
