The lab: Zwart group

The Netherlands Cancer Institute

Lab's research themes:

Our research is focused on epigenetic regulation in hormone-driven cancers. We integrate clinical trials with functional genomics and endocrinology, to identify mechanisms of therapy resistance and reveal novel therapeutic possibilities for companion diagnostics.

Hormonal therapies represent the first and most successful targeted therapies in cancer. In most breast and prostate cancers, hormonal therapy forms the very backbone of systemic treatment. However, resistance to therapy is common, and many patients relapse despite treatment. Our group studies hormonal action in multiple tumor types: endometrial cancer, lung cancer, breast cancer and prostate cancer. Our ultimate goal is to better understand hormonal signaling and elucidate therapy resistance in cancer, contributing to more personalized treatments, the identification of novel therapeutic options and minimizing over-treatment.

Merits of the lab:

As our lab philosophy, we bridge clinic and basic research, to accelerate clinical translation and ensure clinical validity of our findings. As main focus area, we study hormone action in cancer, in relation to the 3D genome and epigenetic mechanisms that dictate hormone action. We developed and refined innovative genomics technologies that enable us to chart the genome-wide action of transcription factors in small amounts of tumor tissue, and pioneered in implementing these technologies in (neoadjuvant) clinical trials.

As an intrinsic component of our lab strategy, we heavily invested in computational biology, functional genetic screens and drug repurposing strategies, creating a full-circle scientific environment geared to foster new exciting and clinically-relevant discoveries. For further background, see the lab’s website or https://pubmed.ncbi.nlm.nih.gov/?term=zwart+w&filter=years.2003-2022.

Why do we want medical doctors?

We have a highly diverse and international team, housing biologists, computational scientists, molecular endocrinologists as well as clinicians. Our team is very closely connected to clinical research labs within the institute as well as (inter)nationally, providing the best possible training environment for clinician-researchers.

Country: The Netherlands
Supervisor: Wilbert Zwart
Research group website

The position

What’s the main purpose of our research?

We study hormone action in multiple tumor types; breast cancer, prostate cancer, endometrial cancer and lung cancer. Our ultimate goal is to better understand hormonal signaling and elucidate therapy resistance in cancer, contributing to personalized clinical decision-making, optimized treatment selection, identification of novel therapeutic options and minimized over-treatment. Hormone receptors are under tight epigenetic control and impacted by the genetic context in which the tumor develops and progresses. By untangling this complex (epi)genetic interplay of hormone receptor biology with its environment in situ, and understanding how this is impacted by treatment, we aim to directly contribute to fully tailored endocrine treatment selection in the future, selecting the most suitable therapy for the individual patient.

How we will do it?

We design our research as a full-circle strategy; starting from clinical observation, towards functional genomics and mechanistic studies in advanced model systems, and back again to the clinic. This involves clinical sample handing, molecular pathology, wet-lab and dry-lab genomics analyses, drug screens and ultimately the design of new clinical trials.

Why is this important?

Resistance to therapy is quite common in cancer patients while it is the very backbone of current systemic treatment for many cancer such as prostate, breast and lung cancer. Therefore, it is important to better understand the development of resistance and explore new therapeutic options. By embedding our research within ongoing and future clinical trials, we directly contribute to finding a solution to this urgent clinical problem.

Who is a good fit for the project?

The ideal candidate has both wet-lab and dry-lab research experience. Most importantly, the candidate should have a keen drive to learn new techniques and proactively engage with other research disciplines.

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