16 Aug 2022

Cancer is too clever to be stopped by a silver bullet

© *Photo by Visualisierung Universitäts-Kinderspital Zürich – Eleonorenstiftung

Our understanding of cancer has improved significantly in recent years, says Prof. Michael Grotzer. But new approaches to fight cancer invasion are still urgently needed. The startup Invasight, which was founded by Grotzer’s former Ph.D. student Karthiga Kumar, has found a promising method.

Prof. Dr. Michael Grotzer
Medical Director, University Children’s Hospital, Zurich

Since 2018, Michael leads Zurich’s University Children’s Hospital, Switzerland’s biggest center for pediatrics and pediatric surgery, which employs 2500 people. Since 1868 the hospital is sponsored by the foundation the doctor Conrad Cramer established for his late wife Eleonore.

Michael did his habilitation in pediatrics with a specialization in oncology in 2002. Since 2018, he is a Full Professor for Pediatrics at the University of Zurich. Michael has received several awards (including the SIOP Award and the Georg Friedrich Götz-Prize) and is a member of a variety of associations. A new building for the children’s hospital (designed by Herzog & de Meuron) is currently under construction. The goal is to finance CHF 125 million of the total cost of around 680 million by private donations.

You have more than three decades of experience in medicine and are specialized in oncology. How has this field and our knowledge of cancer evolved?

We have made a lot of progress in understanding and mapping distinct types of cancer. Tumors might look the same under a microscope, but we can analyze them rapidly on a molecular-biological basis. We have also gained a clearer understanding of how a primary tumor differs from metastases or recurrent cancer, and how the metastatic spread of cancer in the body progresses. This insight is quintessential for successful therapy. Furthermore, we now have a much larger choice of more specific drugs, which is commonly known as personalized medicine.

How high is the chance to survive cancer today?
I can give you a few figures from my work with children and adolescents. On average, the chances of recovery are around 70%. If we look at the most common childhood cancer called acute lymphoblastic leukemia, it is over 80%. In the case of brain tumors, however, the success rate is still an unsatisfactory 60%, although this is better than in adults.

You talked about the advances in cancer medicine. What are the current challenges?
Hospitals still struggle to organize smart clinical trials that help specific patient groups with different combinations of drugs. I expect to see a lot of progress in this regard. In general, the dynamism of cancer research and the wealth of new knowledge can be overwhelming for some hospitals. It would make sense to centralize the treatment of cancer types in fewer hospitals across Europe. Such specialization and division of labor would allow to speed up new clinical trials.

“The way how cancer cells react with the tissue around them is a highly complex and dynamic process.”

Almost all cancers are invasive, which means that they spread across the body and form metastases. Stopping this process is what several cancer drugs aim to do. How well do they perform?

The way how cancer cells react with the tissue around them is a highly complex and dynamic process. Modeling this process on a cellular level is essential to rapidly test new drugs. Today we understand better how the signaling pathways in cancer cells work. Years ago, the understanding was that as soon as we block pathways that are active in cancer cells, the problem is solved. But this initial euphoria gave way to disillusionment. The inhibitor drugs we have aren’t specific to cancer cells, they can bind to other receptors, which leads to a cascade of negative effects we don’t control. Some pathways are redundant, blocking them allows the cancer cells to find other ways to do their harmful effect. Cancer is too dynamic, too clever to be stopped by a silver bullet. Therefore, we need to find ways to stop cancer invasion that cannot be easily circumvented by cancer cells and which don’t have severe side effects.

This brings us to the work of Invasight, a startup that aims to develop a new form of cancer signaling pathway inhibitors. Why do you think their approach is promising?

The founder Karthiga Kumar started her research on the most common malignant pediatric brain tumor called medulloblastoma. She found a fundamentally new starting point to develop new therapies that center on a signaling pathway that is active not only in this but several different important types of cancer, including stomach, colon, and ovarian cancer. The proposed way of action, a protein-protein interaction inhibitor, does not, like current kinase inhibitors, affect the pathways of healthy cells and therefore shows almost no off-target toxicities.

You first met Karthiga Kumar when she started as one of your Ph.D. students at Zurich’s Children Hospital. Does she have the drive necessary to lead a startup in this field?

I remember that one of the first things she said is that she wanted to start a company one day. I thought it’s nice to have dreams, but you need to prove yourself first. She then went on to do research work in quality and quantity I have never seen before. I don’t know how many hours of sleep she gets……which is the same thing that I thought when I was looking at your biography.

I sleep like a baby (laughs). But seriously, if you find purpose in what you do, if you have fun at work, this is a huge motivator and stimulant.

So you said Karthiga was an outstanding Ph.D. student. 
Yes, I am enthusiastic about her persistence, her ability to solve problems and to come up with breakthrough solutions in several fields. Just as an illustration, she wasn’t happy with the pipetting process in our lab and improved it to the point where we filed a patent for it. She also had a clear vision from the beginning and did an MBA on the side during her Ph.D. Now oncology is a very competitive field, and it takes a lot of persistence to come to a result, but I’m convinced that if someone manages, it’s Karthiga. I have even backed up my opinion of her by investing private money in her company.

What would you say is the biggest risk for an investor in such a company?
Invasight has developed a model to simulate and test the metastasis of cancer. This allows testing a very large number of new drug candidates rapidly. The startup is still in an early phase, but the approach has been proven to work. For me, the biggest risk going forward is financing risk, if the startup is able to attract enough money to bring its lead candidate to the end of phase I of the clinical trials. But Karthiga is very convincing and has already taken the first hurdles because it is a brilliant story with many elements that reassure investors.

“The startup is still in an early phase, but the approach has been proven to work.”

The Children’s Hospital is currently also fundraising for its new building that is already under construction. How is the donation drive going?

We’re very confident that we’ll hit our target of CHF 125 million by private donations. We have first approached foundations and wealthy individuals, and just recently started our public campaign which has shown how well the hospital is anchored in the population. The new building will increase our capacity by 30-40%, with more operating rooms, intensive care units and more space for research and teaching right next to the clinic. Because of covid-related supply chain issues – at one moment basic supplies like gypsum binding agents weren’t available – we’ll relocate in fall of 2024, one year later than planned. But the patients and their families will find a hospital that doesn’t feel like a hospital, with plenty of wood used for construction, with pleasant rooms with more privacy. I think it will be Europe’s most attractive leading Children’s hospital.

Written by
Eugen Stamm