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

Breast cancer is the most common cancer in women worldwide. Metastasis, the process by which cancer cells spread to other parts of the body, makes treatments less effective. It is important to unravel the mechanism of metastasis.

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.

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

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

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

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…

PhD student Esmee Koedoot studied the underlying processes responsible for metastases in a dangerous type of breast cancer. She hopes to find new possibilities to fight the disease. In December 2019 she obtained her doctorate cum laude.

To improve treatment of breast cancer patients it is important to understand all stages of breast cancer from initiation to in situ disease and progression to invasive disease. In this thesis we use intraductal injections of patient derived tissue to model ductal carcinoma in situ and invasive breast…

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

Discovery of metastasis promoting candidate drug targets

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.

Promotor: A.H. Meijer, Co-promotor: B.E. Snaar-Jagalska

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

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…

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.

Researchers at Leiden University have mapped genes that cause breast cancer cells to migrate. The Leiden toxicologists Professor Bob van de Water, Dr Wies van Roosmalen, Dr Sylvia E. Le Dévédec and colleagues studied 1500 individual genes. They found eight, including the SRPK1 gene, that regulate the…

Promotor: T. Schmidt, Co-Promotor: B.E. Snaar-Jagalska

In this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer.

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

ᅟ

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.

Prostate cancer (PCa) is one of the most prevalent cancer in males.

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

The immune system plays a paradoxical role in the spread of breast cancer. Some immune cells contribute to metastasis, while other cells can be activated to strengthen the effect of chemotherapy. Kelly Kersten made this discovery in her PhD research. PhD defence 7 February.

In breast cancer, metastasis rather than the primary tumour is the cause of death. A lack of oxygen in the tumour cells promotes this metastasis, accompanied by a reprogramming of the cell's metabolism. PhD candidate Qiuyu Liu investigated these alterations to get more knowledge about the actionable…

What are the biological effects of Chinese herbal medicine in regulation of cancer cell metastasis?

Cell adhesion signaling

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

In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).

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.

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 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…

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…

Mechanisms fro drug resistance

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…

This project is funded by the Dutch Cancer Society. The project will be part of an ongoing research line aimed at identifying mechanisms of cancer therapy resistance and metastasis. In this project, it will be investigated how the Grainyhead family of transcription factors controls therapy response…

PhD defence

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…

In this project, we aim to obtain a quantitative understanding of the role of the immune system in tumor regression, of the role of tumor cell heterogeneity in cancer growth and of tumor cell migration properties.

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

Cell biologist Erik Danen has been awarderd a grant of half a million euros to study how tumor cells spread throughout the body en develop drug resistance. This was announced mid-August by the Dutch Cancer Society Fund (KWF).

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.

This thesis investigates how cell shape and collective behavior influence the dynamics and structure of biological tissues, which are crucial for understanding processes like embryonic development, tissue regeneration, and metastasis.

Can the conditioning paradigm be used for checkpoint inhibition cancer treatment?

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.

This thesis represents a comprehensive investigation into the control of cancer stemness and metastatic initiation using a combination of advanced zebrafish xenograft models and in vitro assays.