In the nineteenth century a Scottish army officer and doctor, George Beatson, discovered a link between hormones and breast cancer. He demonstrated this using cows: to have them produce milk for their whole lives, their ovaries were removed.
He used this 'farmer's common sense' to carry out a test on a small number of women with breast cancer. When Beatson removed their ovaries, the tumour disappeared. In the years that followed this became the standard treatment for women with advanced breast cancer. "He should have been given the Nobel prize for it," claims Zwart.
Another doctor, the Canadian Charles Huggins, proved the existence of a link between hormones and prostate cancer, and in a similar way: after castration, the tumour disappeared. "And he did get the Nobel prize for that," Zwart points out.
Wilbert Zwart is citing Beatson and Huggins' groundbreaking work for good reason. Zwart is a biologist, and his specialism at the Netherlands Cancer Institute (Nederlands Kanker Instituut, NKI) is to identify custom-made treatments for breast and prostate cancer using 'anti-hormones': substances that inhibit, suppress, or even halt the function or production of oestrogen and testosterone, hormones that can be a 'doping agent' for the tumour.
"In breast cancer and prostate cancer, the cancer is often hormone-regulated," explains Zwart. "It's too technically complicated to explain briefly here, but basically a breast tumour uses oestrogen receptors - think of receptors in cells as luggage carriers - to survive and grow. And in the same way, a prostate tumour is 'addicted' to testosterone."
On his office desk stands a rather conspicuous knitted cactus with toothpick spines: a gift from a doctoral student who felt that the department needed to take better care of its plants. More relevant to Zwart's work are the two lumpy pieces of plastic he points out. "The oestrogen receptor, in breast cancer, and the androgen receptor, in prostate cancer. From a 3D printer." They are the root of the evil that Zwart's work and research are fighting: "They're the two most common forms of cancer in the world."
He happens to share the office with the internist and oncologist André Bergman, whose specialism is also prostate cancer. "André has direct experience with patients. Our collaboration takes me into the clinic as well as the research lab - and that enables me to make my research as relevant as possible. Our findings and experiences can strengthen each other."
Zwart has been creating other cross-links too. For almost a year he has been an endowed professor of Functional Genetics in Oncology at TU Eindhoven, a position which he hopes will help him to develop new hormone treatment techniques. He is also working with an American colleague researcher on a project in which breast cancer cells are tested outside the body for drug susceptibility (see box). Last month the NKI was awarded over two million euros' worth of research funding by the Dutch Cancer Society (KWF Kankerbestrijding), of which over half a million euros is intended for another project that Zwart is coordinating: research into a receptor for lung cancer. Collaboration and cross-fertilisation: these are key concepts. "Your own bubble has its limitations," agrees Zwart.
"This work is like top-class athletics. You have to give your best performance. You have to work with all your passion, and with utter dedication. We owe it to the patients. It's the only way to do really good work."
"We have two small kids at home now; they're two and four. Before they were around I could easily put in a working week of 60 or 70 hours. It's less than that now, but once the kids are in bed I grab the laptop again. So does my wife, actually, who's a researcher in jurisprudence. That's how we spend our evenings, sitting together on the sofa and working. We met during my doctoral research. She's never known me any other way. This is my mission."
"I was 18 when my mother died of cancer. That's the foundation of my calling. I grew up in Putten, in the Veluwe. My father was a forester. We lived in the middle of the woods. I was fascinated by everything to do with life. I studied biology at Utrecht, but after that I wanted to join the NKI."
Zwart first joined as an intern. When a doctoral position in breast cancer research became available, he saw his opportunity to stay. "And then, suddenly, you're where you most want to be. I often compare it here to a big beehive: you're constantly bumping into one another, exchanging knowledge, sharing, and helping each other."
Its only recipient outside the US, Wilbert Zwart has been given an ASPIRE Award. The American Mark Foundation is giving him €154,000 to research into the culture of metastatic breast cancer cells on a 3D-printed substrate.
How these cells react to certain medicines will hopefully then predict how the patient, from which these cells were taken, will also respond. In this project Zwart will work together with Luis Solorio of Purdue University, who made the substrate.
"Our research will compare the behaviour of the cells on the 3D matrix with the results of the patient's treatment," explains Zwart. "If the technique works, it could make a real difference to clinical settings. You could also do excellent research into the biology of metastatic cancer."
Doctors can prescribe a variety of drugs when a breast cancer patient has metastases - but what is the best choice of drug? "You don't always know in advance which drug will work best for a given patient," says Zwart. "So there's a clear need for tools that can help us make better choices."
The Netherlands Cancer Institute (Nederlands Kankerinstituut, NKI) is the research institute of the Antoni van Leeuwenhoek hospital. The Institute works to better understand cancer in order to identify better treatments. The NKI in Amsterdam is one of Europe's top ten Comprehensive Cancer Centres: centres that bring cancer care and cancer research under one roof.
Over 700 scientists work at the NKI. Wilbert Zwart is a biologist there, but he is also an endowed professor in the biomedical faculty of TU Eindhoven. He also works for the Oncode Institute and for the Dutch Cancer Society (KWF Kankerbestrijding). He lives in the Zaan area.
In recent years Wilbert Zwart's research team at the NKI has identified several 'biomarkers', biological attributes that can predict the course of an illness or susceptibility to certain drugs. For instance, the team discovered a set of nine genes that help them to predict what will happen to prostate cancer patients and whether they will respond to hormone therapy, which is a treatment option they do not currently receive.
This is an article from Noordhollands Dagblad, Robbert Minkhorst.