What do you consider the most formative phase of your research career?

My work as a PhD student under the guidance of Alex van der Eb. He introduced me to ‘functional genomics’ and oncology research. I have used functional genomics in oncology research ever since I started my PhD research 45 years ago.

What do you see as the most important developments in your field in the past decades?

The elucidation of the human genome sequence and the subsequent identification of mutations in cancer, enabling personalized medicine. Obviously, the second major development in oncology was the realization that we can help the immune system to recognize cancer cells through the use of so called checkpoint blockade therapies (PD1; PDL1; CTLA4 blocking antibodies). These two developments have brought major improvements in the clinical management of a variety of cancers.

Tell us about one of your favourite published papers from your lab.

Two papers from my lab have changed the clinical management of cancer globally; I am very proud of both.

First, we showed in 2002 that a signature of 70 genes, later known as MammaPrint, can predict risk of recurrence in breast cancer. This signature is now used globally and helps reduce the use of chemotherapy for women with early breast cancer.

Van de Vijver, M.J., He, Y.D., van ’t Veer, L.J., Dai, H., A M Hart, A.A.M., Voskuil, D., Schreiber, G.J., Peterse, J.L., Roberts, C., Marton, M.J., Parrish, M., Atsma, D., Witteveen, A., Glas, A., Delahaye, L., van der Velde, T., Bartelink, H., Rodenhuis, S., Rutgers,E. Th., Friend, S.H. and Bernards, R.. (2002). A gene expression signature as a predictor of survival in breast cancer. New England J. Med. 347, 1999-2009.

Second, we showed in 2012 that BRAF inhibition in BRAF mutant colon cancer does not work because the EGFR also needs to be inhibited in this cancer type. This resulted in clinical trials combining BRAF and EGFR inhibitors in BRAF mutant colon cancer. This combination became FDA and EMA approved in 2020.

Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R.L., Bardelli, A., and Bernards, R. (2012). Unresponsiveness to BRAF(V600E) inhibition of colon cancer through feedback activation of EGFR. Nature 483, 100-103.

What’s exciting in your research area right now?

Finding highly synergistic cancer drug combinations based on a mechanistic insight into the vulnerabilities of cancer cells. Many drug companies put little effort in finding the best combinations of their drugs. As one example, there are over 10,000 trials combining PD1 or PDL1 antibodies with nearly every other drug. That is not very intelligent and exposes a lot of patients to toxicity. Rational combinations based on an understanding of why these drugs are synergistic is a more efficient approach to bring drug combinations to the clinic, as our own work has shown also.

What’s currently your favourite technique?

CRISPR genome editing to find functions of genes.

What do you see as the main ‘impacts’ of research in your field?

Patient benefit is the dominant impact of cancer research in the end.

What aspects of recent research in your field should be added to student courses?

The complexity of cancer as an organismal disease, including how the tumor microenvironment contributes to the responses of cancer cells to treatment. It is increasingly evident that there is a dynamic interplay between tumor cells and their direct environment. Tumors can create an inflammatory microenvironment or an immunosuppressive state, depending on the cytokines they release. This has major consequences for how to treat the cancer and should be taken into account when considering treatment options for the individual patient.

What aspects of your life as a researcher do you most enjoy?

Discussing experiments and new questions with my students.

What do you look for when selecting students and staff for your research group?

Motivation and drive; creativity; social skills.

What do you see as the key ingredients for successful research collaborations?

Being generous to your collaborator!

What comes first: technique or biological question?

No doubt, the biological question comes first, and then you select the technique to answer that question. I have always developed new technology only because I could not answer a biological question with the existing technologies.

Lab webpage: https://www.nki.nl/research/find-a-researcher/groupleaders/rene-bernards/

Two recent/key papers:

Dias, M.H., Friskes, A., Fernandes Neto, J.M., van Gemert, F., Mainardi, S., Kuiken, J., Jin, H., Lieftink, C., Mourragui, SW., Papagianni, C., Morris, B., Dekker, A., van Dijk, E., Wilms, L.H.S., sa Silva, M.S., Jansen, R.A., De Conti, G., Mulero Sanchez, A., Malzer, E., Raaijmakers, J., van Tellingen, O., Te Riele, H., van Oudenaarden, A., Kovach, J.S., Beijersbergen, R.L., Villanueva, A., Medema, R., and Bernards, R. (2024). Paradoxical activation of oncogenic signaling as a cancer treatment strategy. Cancer Discovery 14, 1276-1301.
https://doi.org/10.1158/2159-8290.cd-23-0216

Jansen, R.A., Mainardi, S., Henrique Dias, M., Astrid Bosma, van Dijk, E., Selig, R., Albrecht, W., Laufer, S.A., Zender, L., and Bernards, R. (2024). Small molecule inhibition of MAP2K4 is synergistic with RAS inhibitors in KRAS mutant cancers. Proc. Natl. Acad. Sci. USA. 121, e2319492121.
https://doi.org/10.1073/pnas.2319492121

More information on the Molecular Oncology Lecture at the FEBS Congress

René Bernards will deliver the Molecular Oncology Lecture at the 49th FEBS Congress in Istanbul, Türkiye, on Wednesday 9 July 2025 on “Thinking differently about cancer treatment regimens”.

Photo by Milad Fakurian on Unsplash.