Promoting Senescence to stop Tumor Growth

The value of research increases when it is shared. That is why at the UMCG we try to make our publications as open as possible by adhering to the principles of open science. Nearly all our new publications are Open Access. Open science, however, goes further, by attaching value to making data openly accessible, communicating research outcomes to a lay audience more widely, and by rewarding reproducibility studies.

The Open Science Publication of the Month August is “Pharmacological CDK4/6 inhibition reveals a p53-dependent senescent state with restricted toxicity” by Boshi Wang, Marta Varela-Eirin, Simone Brandenburg, Alejandra Hernandez-Segura, Thijmen van Vliet, Elisabeth Jongbloed (Department of Medical Oncology, Erasmus UMC Rotterdam), Saskia Wilting(Department of Medical Oncology, Erasmus UMC Rotterdam), Naoko Ohtani (Graduate School of Medicine, Osaka City University, Osaka, Japan), Agnes Jager (Department of Medical Oncology, Erasmus UMC Rotterdam), and Marco Demaria. We interviewed dr. Boshi Wang about this publication.

Stopping cell division without adding to tumor growth

What are the most important findings of the publication? Boshi: ”We focus on the subject of cancer, but in this project we focused on the normal cells in the tumor microenvironment. We focus on senescent secretory phenotypes. Senescence means the cell is no longer dividing. But even though they are no longer dividing, the cells stay metabolically active. This means the cells secrete inflammatory substances that can harm neighboring cells and add to tumor growth. This is a common problem when conventional DNA-damaging cancer therapies are used and detrimental senescent normal cells are induced in the tumor microenvironment.”

Innovative ways to treat people with cancer is one focal points of the UMCG. This research and publication fit very well within that because the findings of dr. Boshi Wang and his fellow researchers will very likely lead to clinical applications. Wang: “Many of the medicines we use in cancer therapy in order to induce this senescent state lead to the secretion of inflammatory substances. However, we have found that the CDK4/6 inhibitor-induced senescent normal cells, while still partially leading to the secretion of substances, do not contribute to tumor growth.”

Towards clinical application

At the UMCG, we are very aware of our responsibility to make sure we don’t just do state-of-the-art research, but that we also have a positive impact on society through our research. The timeline for this, from developing a new technique to clinical application, is often a long one. However, in this project, clinical application could come about relatively quick. Dr. Boshi Wang: “When we started this research, the medicine that induces senescence without contributing to further tumor growth, was already approved in the US. These medicines are called CDK4/6 inhibitors.” Approval of medicines is a very lengthy process, the fact that these medicines have already been approved in the US and EU will make clinical use a much more timely process.

In order to have a positive impact on society, the research will need to move from the fundamental end to the applied end of the spectrum. For dr. Boshi Wang this means potentially applying his method in clinical settings. Dr. Wang: “I am doing a follow-up study where I treat senescent cells induced by chemo-therapy with this CDK4/6 inhibitor, and there I could also see this reduces secretory phenotypes. For me, my main scope with this research is clinical application. If I can translate my fundamental research into clinical trials, I would be very proud. This medicine is already very well-known with experts in the field of senescence, and being widely used in clinical settings, so we can already see a societal impact there.”