Mechanisms fro drug resistance

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

Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization correlate with proliferative capacity and invasiveness of cancer cells. These changes expectedly lead to altered…

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…

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.

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.

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

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. The University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP) work…

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

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…

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

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

Leiden University Medical Center (LUMC) has spent the past five years coordinating an international study of genetic mutations and breast cancer risks. The results will make it easier to determine which genes increase the risk of breast cancer and to what extent. The researchers published their results…

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

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

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.

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…

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.

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.

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’),…

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.

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.

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.

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. The network is embedded in the Leiden Centre of…

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

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

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…

Discovery of metastasis promoting candidate drug targets

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

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

One of the stained glass windows in the Great Auditorium of the Academy Building is dedicated to the students and staff of Leiden University who resisted, protested against, or became victims of the German occupiers. It depicts female figures alongside male ones.

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

Is is possible to better predict the validity of drug candidates?

Supervisor: Indira Nederpelt

This project will construct an inventory of possible conceptions of the resistance of the world to scientists’ claims and theories.

Promotores: J. Jonkers, K.E. de Visser

Breeding for resistance becomes more and more important because we want to reduce the use of pesticides. A fast and cheap alternative can be to make use of morphological or chemical markers.

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.