Mechanisms fro drug resistance

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…

In this research group, headed by Bob Van de Water, cell signaling programs that underlie adverse drug reactions as well as cancer development and progression are unraveled. Adverse drug reactions involve cell injury in critical target organ cells which leads to the activation of cellular stress response…

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.

In this research group, headed by Prof. Erik Danen, the aim is to unravel cellular signaling mechanisms in normal and diseased cells, with a long-standing interest in cell adhesion signaling. In complex multicellular organisms such as ourselves, a division of labor emerges where different tissues and…

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.

Can effective synergists be identified to enhance the effect of antibiotics against Gram negative pathogens?

There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. Leiden University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP)…

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

The research within the Division of Cell Systems and Drug Safety, headed by Prof. Bob van de Water, is focused on novel therapeutic modalities and novel concepts in early drug discovery, in order to develop more effective and safer therapeutic strategies. We generate advanced cell and computational…

How can zebrafish research help to understand and fight human cancer?

With cancer, a person’s body cells grow uncontrollably. Putting together a detailed picture of how this comes about makes it possible to develop efficient therapies. Researchers at the Leiden University Medical Centre (LUMC) and Leiden University are working together to gain a better understanding…

Research in this group, headed by Gerard van Westen, focusses on computational methods integrated in different parts of the drug discovery process. More specifically, topics include innovative treatments for cancer, selectivity modeling, translational research, allosteric modulation, drug resistance…

Promotor: R.C.M. Pelger Co-Promotor: G. van der Pluijm

How to identify patients at risk of developing devastating, metastatic disease and facilitate the development of personalised treatment for prostate cancer patients?

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

PhD defence

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

What distinguishes a tumour cell from a healthy cell? Researchers are trying to answer this question as precisely as possible. Certain differences could eventually lead to new therapies.

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

In this thesis, we aimed to better understand the underlying mechanisms involved in TNBC progression and metastasis formation and discover new targets to reduce breast cancer related deaths.

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

In the Drug Research theme, we primarily work with rodents. Rodents, such as mice, are one of the most common laboratory animals. These small mammals are easily housed and exhibit a rapid rate of reproduction.

Some people are predisposed to develop cancer. Mutations in genetic material that increase a person’s chances of developing cancer can already be present at birth. Researchers are closely examining these mutations to learn more about how cancer begins to develop.

Cancer represents a formidable current and future global health challenge. The LUMC medical research profile Cancer Pathogenesis and Therapy charges this challenge by developing and implementing innovative patient-tailored, multimodal diagnostic methods and treatment modalities.

The master's specialisation Drug Discovery and Safety at Leiden University provides students with research-oriented education into the discovery of new drug targets and new lead molecules, particularly in the field of cancer, through a combination of advanced imaging techniques (‘systems microscopy’),…

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

Knowledge of mental distress and resilience factors over the time span from before to after a stressor is important to be able to leverage the most promising resilience factors and promote mental health at the right time. To shed light on this topic, we designed the RESIST Study, in which we assessed…

Despite recent advances in medicine, many devastating disorders like cancer and cardiovascular, neurodegenerative and infectious diseases still lack effective treatments. In order to address this challenge, we, as scientists from Leiden University, joined hands in the LED3 network. LED3, for Leiden…

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To inhibit proteins that contribute to the growth of aggressive cancer cells, that’s the plan of Professor Bob van de Water and his team. They will receive over 700,000 euros from the KWF Dutch Cancer Society for their research. Researcher Maaike Vreeswijk and pathologist Danielle Cohen are affiliated…

As of April 1, 2018, Erik Danen has been appointed as Professor of Cancer drug target discovery at the Leiden Academic Centre for Drug Research (LACDR). His discipline is cell biology of cancer, in which he focuses on the mechanisms underlying metastasis and therapy resistance.

Improving healthcare with our scientific discoveries: that is the goal of pharmaceutical research at Leiden University. And there’s a lot involved in that. Our research starts with the discovery of the effect achieved by a particular substance, and sometimes continues all the way through to the development…

In this thesis, we will utilize embryonic zebrafish tumour models to understand the interaction between engrafted human cancer cells and macrophages from the host, test drug administration modalities and anti-cancer efficacies of newly-developed PDT and PACT compounds, and test a light-triggered liposomal…

Promotor: Prof.dr. B. van de Water, Co-promotor: E.H.J. Danen

Promotor: E. Bouwman, Co-promotor: S. Bonnet

Cancer is the leading cause of death in the Netherlands, and, with over 100 different types of cancer, it’s not a simple disease. Today, skin, breast, lung, prostate and colon cancer are the most diagnosed forms. Therefore, the discovery and development of new drugs has the ability to significantly…

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics.

Can metabolomic profiling be used to predict resistance against insect herbivores in plants?