Early dream sparked to help cancer patients
Growing up in mainland China, Fiona decided very early on she wanted to become a doctor. She first became interested in doing so after one of her closest friends at primary school passed away from leukaemia. Dying at just 11 years old, her friend's death had a profound impact on Fiona because it seemed to happen so fast and without her showing any noticeable symptoms. This happened in the 1970s when leukaemia treatment was still very limited. The death of her friend was especially traumatic for Fiona because she had spent nearly every day walking with her to and from school. From then on Fiona decided to devote her life to medicine so that she could find a way to cure leukaemia.
Fiona's parents were academics but had no medical background. They, however, were very supportive of her dream. It also helped that Fiona herself really enjoyed science at school, particularly physics, chemistry and maths. By 1995 Fiona had completed a medical degree at Nantong Medical University and then trained to become a clinical oncologist. Her decision to go down this route was highly unusual because at that time radiation oncology was not a particularly attractive career path. Many were put off going into the field because it involved an extra five years of extra specialty training. Also there were not many places that had radiotherapy machines which meant jobs in the area were scarce. But Fiona believed radiation therapy offered a powerful avenue to treating leukaemia.
It soon became clear to Fiona, once she began treating cancer patients at Nanjing 81 hospital, that achieving a cure was far more complex than she originally anticipated. Not only did it open up her eyes to the many different types of cancer, it also showed her that wider socio-economic factors also played an important role in determining what treatment patients could have, which in turn had an impact on the degree to which they improved. She was particularly shocked to discover that in some cases patients could not get reimbursed for their treatment which meant they had to go without. This got her thinking that she needed to learn far more about the whole healthcare system to understand why some drugs got reimbursed and others did not. She was also intrigued why a drug that proved effective in some patients did not work in others and why its side effects were not universally the same across all patients.
Taking the leap to study abroad
With more and more questions burning in her head, Fiona decided she could only begin to address them by leaving her job to go and study abroad. This was a highly ambitious goal because at that time few Chinese students went to university abroad due to the fact that they could not afford such a venture. In addition, her parents did not have the money to support her and were concerned whether she would be able to adjust to the cultural shock of living in a bustling foreign city. Fiona was then living in Nanjing, a historical and mostly academic city, where she spent most of her time studying advances in the medical science field after working in the hospital.
Fiona applied for as many scholarships as she could. She landed being one of six students in China who succeeded that year in obtaining a full scholarship to study in Europe. Armed with the scholarship Fiona chose to take a master's degree in health services research (health economics) at Erasmus University in Rotterdam. Going to the Netherlands opened what Fiona says was 'a huge door' for her because it gave her the chance to study the country's good healthcare management system. This gave her many insights into how drugs get priced and the criteria used to determine which drugs can get reimbursed. It also taught her a lot about how much a patient's disease and treatment is shaped by social and economic forces in society. She also gained an understanding of how industry functions and gets affected by government decisions and the regulatory environment.
After her master's degree, Fiona gained a scholarship from the Imperial Cancer Research Fund (now Cancer Research UK) to do a doctorate in molecular genetics in London. By exploring the molecular genetics of cancer she hoped to gain a better understanding of carcinogenesis, the process by which normal cells get changed into cancer cells, and why some patients respond better than others to certain treatments. London was not only attractive to Fiona because of the research opportunities it offered her, it also gave her the chance to settle down and have a family with her now husband while pursuing doctoral studies.
Moving into translational oncology
Fiona started her doctorate by studying pure scientific research at University College London and then moved over to Queen Mary University of London to pursue more clinical studies. She says she was fortunate to have Professor Frances Balkwill as her supervisor who took her under her wing. Heading up the Centre for Cancer and Inflammation at Barts Cancer Centre, a lot of Balkwill's work is focused on recreating the tumour environment within the laboratory to understand the links between cancer and inflammation - a type of immune response that can encourage cancer cells to grow and survive. Balkwill's expertise is in ovarian cancer, the sixth most common cancer in women, and looking for ways to translate discoveries made at the benchside into better treatments to improve women's chances of surviving the cancer.
As part of her doctorate, Fiona investigated human ovarian surface epithelial cells. Found in the epithelium, a thin lining of tissue, that covers the outside of the ovary, these cells give rise to 90% of ovarian cancer. Fiona was interested in identifying the molecular events that helped to transform these cells into cancerous cells.
During the course of her research, Fiona built up a cell bank system. This included the primary normal epithelial cells, their telomerase-activated immortalised normal cell lineage and the subsequently transformed malignant cells. As part of this work, she helped find a way to improve the methods used to grow and preserve such cells in the laboratory because they have a limited lifespan outside the body. One of the advantages of a cell bank is that it provides a readily available source of cells along the transformation path from normal to malignant cells to be used for medical research and the development of diagnostics and therapies. At that point Fiona says the oncology community was already beginning to shift away from merely diagnosing cancers based on the first location that they were detected in the body to classifying them according to their molecular background.
Following her doctorate, Fiona spent a short time working as a post-doctoral research assistant and then was a postdoctoral researcher for three years at Queen Mary University of London. This gave her time to dissect the molecular mechanism of cancer cell migration which is essential to the spread of cancer in the body. Cell migration is a normal process which helps in the maintenance, defence and repair of the body. Different mechanisms trigger the movement of cells, including chemical and mechanical signals. But the migration process can sometimes go wrong as happens in the case of cancer. Fiona looked at several small signalling molecules known to encourage the movement and invasion of cancer cells. By doing this work she hoped to provide a new approach to both the diagnosis and treatment of cancer.
Juggling a baby with consultancy work
Towards the end of her postdoctoral research, Fiona decided to take some time off to have a baby. Coming from a traditional Chinese background she felt this was important to do as it provided a way to sustain life and pass knowledge to the next generation. She ended up taking two years off (part-time) to look after her child and then began searching for ways she could use all the knowledge she had gained in healthcare system management and cell biology to improve cancer treatment.
It quickly became clear to Fiona that the best path forward was to form her own consultancy company, London Nanjing Life Science. Consultancy work had the attraction that it could be combined with childcare. And just as important it offered Fiona the means to help laboratory researchers patent their discoveries and link them with industry partners who could transform their ideas into a clinical product. It was also ideal because it would give her scope to draw on all the skills and global networks she had built up in the course of her studies. Having worked with many types of people in various countries she could see where the critical gaps were not only between academia and industry but also in different regions. Another advantage she had for doing such work was being able to speak two languages. This meant she was in a good position to build bridges between European and American researchers and the Chinese biopharmaceutical industry and vice versa.
A lot of Fiona's consultancy work consisted of talking to people to understand what challenges they faced and then looking for ways to resolve their problems. She recalls that many of her days were spent watching her 'baby crawling around in the play area' while she was reading on the computer and then typing up summaries of the information to help her clients understand how their knowledge could be translated into a product. Whenever she was asked to help find a partner for a particular project the key challenge was determining where it might be used and what the market appetite was for the final product.
The start of a new venture - developing a drug platform to prevent side-effects from cancer therapy
For Fiona the consultancy work proved invaluable because it taught her a lot about the biopharmaceutical industry and how to raise funds to turn laboratory developments into clinical products. Accumulating a lot of experience from working on lots of different projects she soon began thinking about how she could advance her own ideas for improving cancer treatment. Her thoughts were solidified by two of the projects she took on as a consultant which touched on her own research interests. As a result of this work she managed to buy some of the patents that emerged from the projects.
Paying for the patents out of her savings, Fiona hoped to bundle them together with her own laboratory results to create a new platform to develop new drugs that would help protect patients against the toxic effects of cancer therapy. Her ambition to do this was driven by the terrible side effects she had seen among her first patients. It was not uncommon for her to see patients severely deteriorate after receiving one or two cycles of treatment. The problem was not because the treatment was ineffective, but because it took too much of a toll on the rest of the patient's body. In some cases the cancer treatment can make the patients so sick they find it hard to finish their treatment. This is because alongside killing cancer cells therapy can also damage normal cells.
Cancer has a range of treatments. Which type is given depends on the type of cancer a patient has and also how advanced it is. In some cases one course of therapy is enough, but in most cases patients need a combination of treatments. Each treatment serves a different purpose. Surgery is typically used to remove a specific tumour from the body. This might then be followed up with radiation therapy which is used to kill any remaining cancer cells and shrink tumours. Another way to destroy cancer cells is to use drugs, known as chemotherapy. Then there is immunotherapy which is designed to harness the immune system to fight cancer. Both chemotherapy and immunotherapy are called 'systemic' treatments because they can affect the whole body. Some types of cancer, including leukaemia, lymphoma and myeloma, are also often treated with stem cell and bone marrow transplants. Such treatment helps replace bone marrow cells destroyed by the cancer and or radiation to eliminate the cancer.
Each of the treatments can cause different side effects. In some cases this might only be very mild, but in others it can really affect a patient's quality of life. One of the most visible side effects is hair loss, a condition known as alopecia. This results from the fact that cancer treatment can harm the cells that help hair grow. Hair can be lost from all parts of the body, including the head. For patients this can be very challenging both in terms of their physical appearance as well as emotionally. As well as hair loss, cancer therapy can frequently cause skin problems, including rashes, itching and blisters. While for some patients this might only be mild, in others it can be very distressing.
One of the most debilitating side effects caused by cancer therapy is mucositis, a condition caused by injury to the mucosa. The mucosa is a thin mucous membrane that lines many parts of the body, including the mouth, throat, ears, and also the digestive, respiratory and reproductive tracts. It acts as a protective barrier against abrasion and infection. The membrane is highly vulnerable to damage by radiation treatment, chemotherapy and immunotherapy by virtue of its rapid rate of cell turnover. Such treatments can cause a range of symptoms, including very painful mouth ulcers, difficulties swallowing, eating or talking, a dry mouth and lips, diarrhoea, and bleeding from the bottom as well as pain when going to the toilet. Mucositis can also increase a person's risk of infection due to sores in the mucosa.
Based on her previous research, Fiona wondered whether it was possible to protect patients against common complications associated with cancer therapy by temporarily reducing the blood flow to normal skin and mucosa both before and during their treatment. She believed this could be done by building a platform with a vasoconstrictor, a type of medication designed to narrow blood vessels which could be used in tandem with different cancer drugs. Essentially her idea was to find a way to put the cells in the skin, the hair follicle and mucosa into a sleep mode so they become resistant to damage caused by radiation or drugs. She hoped to achieve this by creating a solution that could be applied topically to the skin and the scalp or used as a mouthwash before and during cancer therapy.
In order to test out her concept Fiona set up a small company in Hong Kong and a subsidiary in China. One of the reasons for her locating the company over there was because it would make it easier to raise funding in Asia. Importantly both China and Hong Kong had good funding for supporting start-up companies to test out new ideas.
Fiona was forced to rethink her strategy by the COVID-19 pandemic. No longer able to travel due to lockdown, she decided the best way forward was to establish another company, VasoDynamics, in the UK. By now her platform had proven successful in a number of early clinical trials such that it was ready to be scaled up for the next stage of development.
Key ingredients for moving forward
Getting the platform developed was not straightforward and involved lots of twists and turns along the way. Taking many years to develop and involving many different partners, Fiona could not have carried on the project without the support of her family and business partners. Without their support, Fiona says, she could not have taken the risks that she has. The challenges have not only been scientific but also about keeping her investors informed and aligned. This has sometimes been difficult because they do not always have the same expectations about the direction of progress and/or speed of return of their investment. But she has so far always managed to keep good communication and move forward, driven by her goal to create a product that will one day benefit patients.
Moving her vision forward is all-consuming for Fiona. As she says every night she dreams about what she has to do the next morning. For her the work is endless, ranging from raising capital to setting up clinical trials and then analysing the results. As a result no two days are the same. What gets Fiona up in the morning is the hope that one day she will be able to improve cancer treatment. She treasures the fact that now she has scope to help more patients than she would have had if she just remained working as a clinical doctor in China treating her own patients.
Small start-up companies - important source of information for anyone considering a career in the biomedical sector
When asked what she would recommend to others thinking of following in her footsteps, Fiona says the most important thing is to follow their passion. Also she suggests talking to as many people as possible in start-up companies. This is because they are highly familiar with the pain and happiness involved in getting an idea off the ground and seeing it through to a clinical product. Often driven by a strong passion, they will also be very open to sharing their experiences and providing guidance. In addition, their experiences are likely to be much more varied than someone who has spent most of their career in a big company where people are more likely to stay in just one department with a very defined role supported by a large surrounding team and are relatively isolated from the practical details of getting something started.
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This article was written by Dr Lara Marks based on an interview conducted with Dr Ningfeng Fiona Li on 12th July 2023.