In Japan, one in two people will get cancer and one in three will die from it. Anticancer drugs play a major role in many of these cancer treatments. In step with recent medical advances, a wide range of anticancer drugs have been developed, and the lives of many patients have been saved. On the other hand, it is also true that anticancer drugs can be accompanied by various side effects.
When the topic of the side effects of anticancer drugs arises, many of us may think of nausea, vomiting, hair loss, and a weakened immune system. In her research, Jonan zeroed in on the damage that anticancer drugs cause to the mucus membranes in the small intestine. The small intestine is considered an important organ for the absorption of nutrients, but surprisingly, diseases of the small intestine have not been fully understood until recently.

Jonan conducted an experiment using an anticancer drug called 5-fluorouracil (5-FU). One side effect of cytotoxic anticancer drugs like 5-FU is that they shorten the length of the villi in the mucus membranes of the intestine and the destroy the cellular structure of crypts (tubular indentations in the villi), thereby reducing the intestinal barrier against bacteria and toxins. This results in side effects such as severe diarrhea and weight loss, and greatly impairs the quality of life (QOL) of patients with cancer.

In her experiment, Jonan first administered 5-FU to mice to create a model of drug-induced enteritis, a condition that mimics small intestinal damage. She also prepared another group of mice that received glutamate before 5-FU was administered. During the experiment, Jonan recorded the mice's weight and fecal condition daily, and then she removed ileum tissue from the mice and conducted histological and biochemical evaluations of the tissue condition.
What she found was that the mucus membranes of the small intestine of mice treated with glutamate demonstrated cell structures that were less damaged than in the group not treated with glutamate.

By getting to the bottom of the essential question of why glutamate is effective against inflammation caused by anticancer drugs, Jonan is conducting research that goes beyond just elucidating the underlying mechanism and includes the patient approach.

A major catalyst that spurred Jonan’s interest in research was an international joint research project with an overseas sister school that she participated in when she was a student at Ritsumeikan Senior High School. For the first three years of high school, she worked with students from a sister school in Taiwan to research butterfly habitat expansion in a project entitled “Adaptive Strategy of Argyreus hyperbius.” Since then, her fascination with research has grown because she experienced the excitement of pursuing inquiry in a global environment, where discoveries generate new questions. She says this experience still lives on to this day.

Jonan decided to go to university to explore pharmacy, a field she has been interested in since she was a child. What inspired her to pursue research on side effects in graduate school was witnessing people close to her suffering from the side effects of cancer. During her practical training at a hospital, she saw a pharmacist proposing measures to one of his cancer patients on how to deal with the side effects they were suffering from, and this made her keenly aware of the importance of assessing drugs for their side effects. Furthermore, her practical training at a medical facility overseas made her realize that side effects are a common issue throughout the world.
Wanting to play an active role in the world, Jonan thought that she could contribute to more people by researching the causes of side effects, so she decided to join Professor Kikuko Amagase's laboratory, which studies gastrointestinal disorders and other side effects of anticancer drugs. According to Jonan, she landed on her current research topic by combining the evaluation of anticancer drug efficacy, which she studied as an undergraduate, with the responsibilities of pharmacists, which she witnessed first-hand during her practical training.

Precisely because her research deals with the evaluation of side effects, Jonan says it is always important to consider whether overcoming those side effects will have an impact on the primary effect of a drug. What’s more, when viewed from a clinical perspective, there is a need to consider the possibility that what is effective in one organ, the small intestine, could cause problems in other parts of the body, such as the heart, liver, or brain. Jonan has a strong desire to not only elucidate functions but also to apply her findings to clinical practice, and she says this is what makes the research interesting even when it raises vexing issues.

Jonan says she has struggled at times with figuring out what kind of research data she needs to collect and what kind of experiments she needs to run to prove her hypotheses. One thing she makes a point of doing is communicating with researchers and graduate students from a diverse array of fields. During the research phase, when she wanted to analyze the function of a protein, she sought advice from a faculty member passing by, and when she was struggling with the method she was using for genetic manipulation, a faculty member she was introduced to lend her a reference book.

Jonan is schedule to work at the Pharmaceuticals and Medical Devices Agency (PMDA) starting in April 2024. PMDA is an organization that aims to improve the health of the people and the level of medical care by reviewing the approval of new drugs, publishing safety information, and providing remedies for side effects and other health problems.

In her research thus far, Jonan has grappled with how to evaluate research data and how it can be applied to future clinical issues. We will root for her as she continues to explore the future of drug development in a new field.