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Anja van de Stolpe

Anja van de Stolpe
  • MD PhD clinical internist
  • Chief Scientific Officer at DCDC Tx

Founder and Chief Scientific Officer at DCDC Tx

About

177
Publications
31,476
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Introduction
Drug development, focus on repurposing drugs, making use of our proprietary Signal Transduction Pathway technology to identify mechanisms of disease (including disease-variants) in patient samples and in preclinical disease models. This enables drug development on preclinical disease models that are representative for the disease in the patient.
Current institution
DCDC Tx
Current position
  • Chief Scientific Officer

Publications

Publications (177)
Article
Full-text available
Sepsis represents a serious disease burden that lacks effective treatment. Drug development for sepsis requires laboratory models that adequately represent sepsis patients. Simultaneous Transcriptome-based Activity Profiling of Signal Transduction Pathway (STAP-STP) technology quantitatively infers STP activity from mRNA levels of target genes of t...
Article
Full-text available
Background/Objectives: Advances in treatment options have barely improved the prognosis of ovarian carcinoma (OC) in recent decades. The inherent heterogeneity of OC underlies challenges in treatment (development) and patient stratification. One hurdle for effective drug development is the lack of patient-representative disease models available for...
Article
Full-text available
For many diseases, including cancer, infections, and auto-immune diseases, the immune response is a major determinant of disease progression, response to therapy, and clinical outcome. Innate and adaptive immune responses are controlled by coordinated activity of different immune cell types. The functional activity state of immune cells is determin...
Article
Full-text available
Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored...
Article
Full-text available
Imbalanced immune responses are a prominent hallmark of cancer and autoimmunity. Myeloid cells can be overly suppressive, inhibiting protective immune responses or inactive not controlling autoreactive immune cells. Understanding the mechanisms that induce suppressive myeloid cells, such as myeloid-derived suppressor cells (MDSCs) and tolerogenic d...
Article
Full-text available
Background Advanced low‐grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predict...
Article
Full-text available
Background: The RAS/RAF/MEK/ERK (MAPK) pathway plays a role in ovarian carcinogenesis. Low-grade serous ovarian carcinoma (LGSOC) frequently harbors activating MAPK mutations. MAPK inhibitors have been used in small subsets of ovarian carcinoma (OC) patients to control tumor growth. Therefore, we performed a meta-analysis to evaluate the effective...
Article
Full-text available
Objective: Ulcerative colitis (UC) and Crohn’s disease (CD) are two subtypes of chronic inflammatory bowel disease (IBD). Differential diagnosis remains a challenge. Anti-TNFα treatment is an important treatment for IBD, yet resistance frequently occurs and cannot be predicted. Consequently, many patients receive ineffective therapy with potentiall...
Article
Introduction: Immunohistochemical expression (IHC) of estrogen receptor (ER) and progesterone receptor (PR) are biomarkers for prognosis and response to hormonal therapy in endometrial cancer (EC). However, the presence of ER/PR is not inherently reflective of estrogen driven tumor growth. Previously, ER pathway activity score (ERPAS), a test to as...
Preprint
Objective Ulcerative colitis (UC) and Crohn’s disease (CD) are two subtypes of chronic inflammatory bowel disease (IBD). Differential diagnosis remains a challenge. Anti-TNFα treatment is an important treatment for IBD, yet resistance frequently occurs and cannot be predicted. Consequently, many patients receive ineffective therapy with potentially...
Article
Full-text available
In this study we aimed to investigate signaling pathways that drive therapy resistance in esophageal adenocarcinoma (EAC). Paraffin-embedded material was analyzed in two patient cohorts: (i) 236 EAC patients with a primary tumor biopsy and corresponding post neoadjuvant chemoradiotherapy (nCRT) resection; (ii) 66 EAC patients with resection and cor...
Article
Important challenges in stem cell research and regenerative medicine are reliable assessment of pluripotency state and purity of differentiated cell populations. Pluripotency and differentiation are regulated and determined by activity of developmental signal transduction pathways (STPs). To date activity of these STPs could not be directly measure...
Article
Introduction: Triple negative breast cancer (TNBC), defined by the absence of expression of estrogen receptor (ER), progesterone receptor, and HER2, is a heterogenous subgroup of breast cancer which currently accounts for a significant proportion of the mortality from the disease. Consequently, there is an urgent need to identify more effective the...
Article
Full-text available
Objective To determine the activity of key signal transduction pathways in serous tubal intraepithelial carcinoma (STIC) and concurrent high-grade serous carcinoma (HGSC) and compare this to pathway activity in normal Fallopian tube epithelium (FTE). Methods We assessed mRNA expression levels of pathway-specific target genes with RT-qPCR in STIC a...
Article
Full-text available
Cancer immunotolerance may be reversed by checkpoint inhibitor immunotherapy; however, only a subset of patients responds to immunotherapy. The prediction of clinical response in the individual patient remains a challenge. CD4+ T cells play a role in activating adaptive immune responses against cancer, while the conversion to immunosuppression is m...
Article
Full-text available
Introduction The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of functional signal transduction pathway activity is important to be able to clarify the role of aberrant...
Article
Full-text available
Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely...
Article
Full-text available
Introduction: Sepsis is a life-threatening complication of a bacterial infection. It is hard to predict which patients with a bacterial infection will develop sepsis, and accurate and timely diagnosis as well as assessment of prognosis is difficult. Aside from antibiotics-based treatment of the causative infection and supportive measures, treatment...
Article
Full-text available
High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, has a high mortality rate. Although there are some factors associated with survival, such as stage of disease, there are remarkable differences in survival among women diagnosed with advanced stage disease. In this study, we investigate possible relations between...
Preprint
For many diseases, including cancer, viral infections such as COVID-19, bacterial infections, and auto-immune diseases, the immune response is a major determinant of progression, response to therapy, and clinical outcome. Innate and adaptive immune response are controlled by coordinated activity of multiple immune cell types. The functional activit...
Article
Full-text available
Multiple myeloma (MM) is a hematological malignancy that is still considered incurable due to the development of therapy resistance and subsequent relapse of disease. MM plasma cells (PC) use NFκB signaling to stimulate cell growth and disease progression, and for protection against therapy-induced apoptosis. Amongst its diverse array of target gen...
Preprint
Introduction Sepsis is a life-threatening complication of a bacterial infection. Accurate and timely diagnosis, as well as prognosis-prediction, is difficult. It is hard to predict which patients with a bacterial infection will develop sepsis. Aside from antibiotics-based treatment of the causative infection and circulation-supportive measures, tre...
Conference Paper
Full-text available
Introduction: The majority of advanced stage high-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, recurs within the first 24 months despite complete remission after initial treatment. Yet there are remarkable differences in disease-free (DFS) and overall survival (OS). We hypothesize that differences in signal tran...
Conference Paper
Background: Primary breast cancer is routinely subtyped using immunohistochemistry (IHC) staining and treatment choice is guided by the subtype. Targeted treatment requires the targeted signaling pathway to be active and tumor driving. IHC staining does not provide reliable information on active signaling pathways, and we reported before that clini...
Article
Full-text available
Objective To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/mTOR biomarkers on therapy response. Methods A systematic search was conducted in PubMed, Embase and the Cochrane Library for articles r...
Article
e17541 Background: High-grade serous carcinoma (HGSC) is the most common subtype of epithelial ovarian and tubal cancer. It has a high mortality rate, even after successful first-line treatment with debulking surgery and chemotherapy. Although therapeutic options for targeted therapy are rapidly expanding, identification of patients who respond to...
Article
Full-text available
Background Around 20% of women with endometrial cancer have advanced stage disease or suffer from a recurrence. For these women, prognosis is poor and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall...
Preprint
Full-text available
Stem cell research is emerging both as a scientifically and clinically relevant area. One of the current challenges in stem cell research and regenerative medicine is assessment of the pluripotency state of induced pluripotent stem (iPS) cells. Once a stem cell differentiation process is initiated the challenge is how to assess the state of differe...
Article
Full-text available
Purpose Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response. To determine the accuracy of ER protein expression...
Article
Full-text available
Targeted therapy aims to block tumor-driving signaling pathways and is generally based on analysis of one primary tumor (PT) biopsy. Tumor heterogeneity within PT and between PT and metastatic breast lesions may, however, impact the effect of a chosen therapy. Whereas studies are available that investigate genetic heterogeneity, we present results...
Article
Full-text available
Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumo...
Article
Full-text available
Activity of the canonical estrogen receptor (ER) pathway is equivalent to functional activity of the nuclear ER transcription factor. Monoclonal antibodies (MoAbs) that identify nuclear ER in cells and tissue samples are frequently used to assess ER transcriptional activity, however, it remains unclear if this approach is sufficiently predictive of...
Chapter
What are drugs? Drugs are substances that can be absorbed by the body to alter cellular behavior and thereby correct abnormal body function, relieve symptoms of the disease, or in some cases even cure the disease. Centuries of medicine as a “profession” in ancient, primitive, and contemporary cultures have led to the discovery of thousands of natur...
Chapter
This chapter is about stem cells: what we can do with them and what they can mean for future health. To begin though, and to distinguish fact from fiction, we have to understand what they are. They are best defined as cells that can divide over long periods but at the same time have the ability to form one or more different cell types through a pro...
Chapter
This book is about stem cells. Stem cells and their applications in clinical medicine, biotechnology, and drug development for pharmaceutical companies involve many facets of biology, from genetics, epigenetics, and biochemistry to synthetic scaffolds and three-dimensional architecture for tissue engineering. For this reason the most important mole...
Chapter
Cancer is a diagnosis still widely feared despite recent developments in excellent treatments and even cures for many types. Understanding cancer stem cells may lead to new ways to tackle the disease. We discuss these very unusual cells in this chapter.
Chapter
Embryonic development has fascinated scientists and philosophers from ancient culture to the present day. Aristotle (384–22 BCE) was among the first to describe the process of fertilization and embryonic development in detail and in his Περι ζωιων γενεσεωσ or De generatione animalium (on the generation of animals), he discussed how a living animal...
Chapter
Making stem cell products available to customers, whether for transplantation as therapy to patients or as specific derivatives of stem cells to pharmaceutical companies for drug testing and discovery, usually requires that there is some opportunity for the manufacturer to commercialize the product and make a profit. If there is no opportunity for...
Chapter
Stem cell tourism is a term recently coined to describe a growing practice among patients to pay large sums of money to private clinics for often unproven stem cell therapies. Patients can be desperate because conventional medicine has failed to provide a solution for their particular condition. For diseases affecting children, emotions may run par...
Chapter
Animals have many of the same ailments and injuries as people so that stem cells could in principle also be used to treat animals with damaged tissues and organs. In fact the potential effectiveness of most stem cell therapies is actually pretested in animals and these studies can therefore be useful for obtaining more fundamental information on an...
Chapter
When pluripotent stem cells were first identified, their ability to divide indefinitely and form all cell types of the body made them in some ways more interesting for both basic research and future therapeutic applications. As far as we knew, adult stem cells had only a limited ability to divide in culture, were difficult to find in the body, and...
Chapter
An exciting multidisciplinary area of scientific research has recently emerged around a new concept now referred to as “organ-on-a-chip.” “Organ” is, of course, clear and “chip” is familiar to many as the miniaturized electrical circuitry in their mobile phone or laptop, but organ-on-a-chip? The term was coined to describe a cell culture-based mode...
Chapter
There is sometimes confusion about the difference between stem cell medicine and regenerative therapy in considering clinical applications of stem cells. There is a widely held perception that stem cell medicine is the same as (stem) cell therapy, which is actually not the case. While cell therapy (meaning a therapy with cells) is certainly a usefu...
Chapter
In this closing chapter, we will take a bird’s eye view of some of the interesting new ideas currently in development that illustrate the diversity of applications that will be enabled by stem cell technology in the coming few years.
Chapter
It is sometimes difficult to say exactly when a discovery was made. Usually information accumulates over a long period of time and suddenly it becomes clear that something has been discovered. Such is the case with embryonic stem cells. These stem cells emerged as a way to explain findings in science and medicine that go as far back as ancient Gree...
Chapter
Cardiomyocytes are the cells in the heart that make it contract. There are several different kinds of cardiomyocytes in the heart. By investigating how they form (or differentiate) in the early embryo, it has been possible to develop ways of making them from some types of stem cell. In this chapter we discuss how they might be used in biomedical, c...
Chapter
A widely used definition of a stem cell is “a cell that can divide to give rise to both a new copy of itself and at least one specialized, differentiated, cell type.” Although this broad definition provides a useful framework, much still remains to be discovered about the different types of stem cells, their shared as well as unique properties, and...
Chapter
One way to obtain immunologically matched stem cells is using a method called therapeutic cloning. This is based on the technique of nuclear transfer, where the DNA of an egg cell is replaced by that of any differentiated “somatic” cell in the body, for example, from the skin. In principle, all cells except sperm or egg cells can serve as the donor...
Article
Full-text available
Background: The Notch signal transduction pathway is pivotal for various physiological processes, including immune responses, and has been implicated in the pathogenesis of many diseases. The effectiveness of various targeted Notch pathway inhibitors may vary due to variabilities in Notch pathway activity among individual patients. The quantitativ...
Article
Full-text available
Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK...
Article
Full-text available
Cancer immunotolerance can be reversed by checkpoint blockade immunotherapy in some patients, but response prediction remains a challenge. CD4+ T cells play an important role in activating adaptive immune responses against cancer. Conversion to an immune suppressive state impairs the anti-cancer immune response and is mainly effected by CD4+ Treg c...
Article
Full-text available
We investigated signal transduction pathway (STP) activity in high-grade serous ovarian carcinoma (HGSC) in relation to progression-free survival (PFS) and overall survival (OS). We made use of signal transduction pathway activity analysis (STA analysis), a novel method to quantify functional STP activity. Activity of the following pathways was mea...
Conference Paper
p> Introduction: Precision medicine has shown to improve outcomes of cancer patients by identifying oncogenic alterations and actionable mutations. Yet, most tests perform DNA sequencing and are not able to discriminate which tumor driving signaling pathways (SP) are functionally active. OncoSignal pathway analysis tests quantitatively measure acti...
Article
Full-text available
Therapy targeting the estrogen receptor (ER) pathway is being explored as a treatment option in ovarian carcinoma. However, studies on the efficacy of anti-estrogen therapy include a broad range of histological subtypes and/or do not select patients based on ER status. This systematic review provides an analysis of literature on the clinical benefi...
Preprint
Full-text available
Background Targeted drug treatment aims to block tumor driving signaling pathways, and is generally based on analysis of one primary tumor (PT) biopsy. Phenotypic heterogeneity within primary and between primary and metastatic lesions was investigated. Methods Activity of androgen and estrogen receptor, PI3K-FOXO, Hedgehog, TGFβ, and Wnt signaling...
Preprint
Full-text available
The Notch signal transduction pathway is pivotal for various physiological processes including immune responses, and has been implicated in the pathogenesis of many diseases including T-cell acute lymphoblastic leukemia. Various targeted drugs are available that inhibit Notch pathway signaling, but their effectiveness varies due to variable Notch p...
Article
Full-text available
Oestrogen receptor (ER) expression is a prognostic biomarker in endometrial cancer (EC). However, expression does not provide information about the functional activity of the ER pathway. We evaluated a model to quantify ER pathway activity in EC, and determined the prognostic relevance of ER pathway activity. ER pathway activity was measured in two...
Article
e15606 Background: Precision medicine refers to tailoring of treatment to each individual patient, although identifying tumor driving signaling pathways (SP) that are functionally active is still a challenge. OncoSignal pathway tests quantitatively measure activity of SP such as estrogen receptor (ER), androgen receptor (AR), PI3K, MAPK, Hedgehog (...
Article
e23558 Background: DF are locally invasive soft tissue tumors of fibroblast origin, with unpredictable course. CTTNB1 mutations are a hallmark of DF. Molecular-targeted therapies are lacking. Recently developed OncoSignal (www.philips.com/oncosignal) pathway activity tests enable quantitative measurement of activity of clinically relevant oncogenic...
Preprint
The host immune response determines the clinical course of a viral infection, for example in case of COVID-19 infection. The effectiveness of vaccination also depends on the induced immune response. Currently there is no method to measure the cellular immune response in blood samples. The functional activity of cells of innate and adaptive immune s...
Preprint
Full-text available
Activity of the canonical estrogen receptor (ER) pathway is equivalent to functional activity of the nuclear ER transcription factor. To assess transcriptional activity of ER, for biomedical research and diagnostic purposes ER monoclonal antibodies are routinely used to identify nuclear ER staining in cells and tissue samples, however it remained u...
Article
Full-text available
: Estrogen receptor positive (ER+) breast cancer patients are eligible for hormonal treatment, but only around half respond. A test with higher specificity for prediction of endocrine therapy response is needed to avoid hormonal overtreatment and to enable selection of alternative treatments. A novel testing method was reported before that enables...
Article
Background: Androgen receptor (AR) immunohistochemistry staining in breast cancer has revealed frequent AR expression in all breast cancer subtypes. Activity of the AR signaling pathway can be either tumor suppressive or tumor promoting, depending on tumor context (Pharmacol Ther., In press, https://doi.org/10.1016/j.pharmthera.2019.05.005). For th...
Article
Background: Based on preclinical research, the MAPK growth factor pathway is thought to be an oncogenic pathway driving breast cancer, potentially in association with the ER pathway. In patients it is unclear how functional activity of the MAPK pathway activity relates to activity of the ER pathway to drive cancer growth. We have reported before on...
Article
Full-text available
Androgen deprivation therapy (ADT) is first‐line palliative treatment in androgen receptor‐positive (AR+) salivary duct carcinoma (SDC), and response rates are 17.6–50.0%. We investigated potential primary ADT resistance mechanisms for their predictive value of clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving pal...
Article
Background: 10-15 signal transduction pathways govern major cellular processes, e.g. cell division, differentiation and migration, both in physiology and pathophysiology. They are frequently abnormally active in cancer and can drive cancer growth and metastasis. Resistance to targeted drugs directed towards specific signaling pathways like the ER p...
Article
Background: The advancement of targeted drugs for blocking tumor driving signaling pathway(s) is expected to lead to improved outcome for cancer patients. However, a critical requirement for that is reliable and accurate diagnostics on activity of oncogenic signaling pathways. A novel analysis method, based on Bayesian network-based inference of si...
Article
Endocrine therapy is important for management of patients with estrogen receptor (ER) positive breast cancer, however positive ER staining does not reliably predict therapy response. We assessed the potential to improve prediction of response to endocrine treatment of a novel test that quantifies functional ER pathway activity from mRNA levels of E...
Article
Background The NOTCH signaling pathway is pivotal for various physiological processes including immune responses, and has been implicated in the pathogenesis in many diseases including T-cell acute lymphoblastic leukemia (T-ALL). Over 70% of T-ALL patient samples contain mutations in NOTCH1 and/or FBXW7 that result in the activation of the NOTCH pa...
Conference Paper
Introduction/Background High-grade serous carcinoma (HGSC) is the most lethal gynecological malignancy due to late detection and high recurrence rates. New treatment options focus on targeted therapy based on signal transduction pathways (STPs). Tumour growth is induced by aberrant STP activation leading to disturbed cell proliferation and differen...
Conference Paper
Introduction/Background The disease-free survival (DFS) of high-grade serous cancer (HGSC) varies greatly, despite comparable clinicopathological features and treatment. It is our hypothesis that the difference in DFS is caused by differences in activity of tumour-driving signal transduction pathways. Methodology Using previously described Signal...
Article
Background To reveal candidate signaling pathways for targeted therapy in esophageal cancer (EC), and esophageal adenocarcinoma (EAC) in particular, we investigated key signal transduction pathways in material available in clinical routine, before and after neoadjuvant chemoradiation (nCRT), and for primary tumor and recurrent disease. Methods Par...
Article
Background Despite ER positive IHC staining, some patients do not respond to neoadjuvant endocrine therapy, suggesting that ER staining lacks specificity to predict response. We developed a method to infer a quantitative signal transduction pathway activity score (PAS) from mRNA levels (microarray, qPCR) of pathway-associated transcription factor t...
Article
Full-text available
BACKGROUND Diffuse Intrinsic Pontine Glioma (DIPG) is a pediatric brain tumor (glioma), resistant to chemotherapy, with only a temporary response to radiotherapy and an extremely bad prognosis. Genomic abnormalities have been found, indicating abnormal activation of certain growth factor signaling pathways, while expression analysis suggests involv...
Conference Paper
Tumor cells can induce immunotolerance, which is reversed by checkpoint blockade immunotherapy in some patients, although response prediction remains a challenge. CD4+ T cells play an important role in activating adaptive immune responses with their conversion to a suppressed state impairing anti-tumor immune responses. CD4+ T cells function by act...
Conference Paper
To improve pathophysiology research, biomarker discovery and drug development, cell culture models should adequately mimic human (patho)physiology and provide reproducible results. This requires comparison between cultured cells/tissue and actual histopathology in the patient, as well as standardization of culture experiments to ensure experimental...
Conference Paper
Tumor cells can induce immunotolerance, which is reversed by checkpoint blockade immunotherapy in some patients, although response prediction remains a challenge. CD4+ T cells play an important role in activating adaptive immune responses with their conversion to a suppressed state impairing anti-tumor immune responses. CD4+ T cells function by act...
Conference Paper
To improve pathophysiology research, biomarker discovery and drug development, cell culture models should adequately mimic human (patho)physiology and provide reproducible results. This requires comparison between cultured cells/tissue and actual histopathology in the patient, as well as standardization of culture experiments to ensure experimental...
Article
589 Background: Treatment with targeted drugs aims to block tumor driving signaling pathway(s). Drug choice is often based on a single preoperative primary breast cancer biopsy. It is important that biopsied cancer tissue is representative for the primary tumor (PT) or metastases to treat. Little is known about pathway heterogeneity within the PT,...
Article
Full-text available
The idea of artificial intelligence (AI) has a long history. It turned out, however, that reaching intelligence at human levels is more complicated than originally anticipated. Currently, we are experiencing a renewed interest in AI, fueled by an enormous increase in computing power and an even larger increase in data, in combination with improved...
Article
Full-text available
The phosphoinositide 3-kinase (PI3K) growth factor signaling pathway plays an important role in embryonic development and in many physiological processes, for example the generation of an immune response. The pathway is frequently activated in cancer, driving cell division and influencing the activity of other signaling pathways, such as the MAPK,...
Article
Background: Immunohistochemistry (IHC) staining for ER and progesterone (PR) receptors in breast cancer tissue is the current standard for testing for eligibility for hormone targeted therapies. However, these markers are imperfect predictors of response, and ER/PR expression can be heterogeneous, especially in the metastatic setting. Within an adj...
Article
Introduction The PI3K signaling pathway is frequently active in triple negative breast cancer (TNBC), but response to PI3K inhibition is still poorly understood. To gain insights in therapy response and resistance, it is important not only to assess genetic alterations of these tumors, but also their phenotypic characteristics. Furthermore, not onl...
Article
Full-text available
Signal transduction pathways are important in physiology and pathophysiology. Targeted drugs aim at modifying pathogenic pathway activity, e.g., in cancer. Optimal treatment choice requires assays to measure pathway activity in individual patient tissue or cell samples. We developed a method enabling quantitative measurement of functional pathway a...
Article
Full-text available
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper
Poster
Full-text available
Background Patient-derived xenograft (PDX) models are becoming the cornerstone of preclinical profiling of anti-cancer agents, facilitating efficacy tests of agents targeting cellular signal transduction pathways. Selecting the right PDX models, usually based on molecular characteristics, is key for the success of such preclinical studies. However...
Poster
Background: Experimental disease model systems, like cell and tissue culture, aim at mimicking tissue (patho)physiology in vitro, for example for (targeted) drug development. This requires comparison between the cell or tissue model and actual pathology in a patient, and quantitative readout of drug efficacy and toxicity. When using stem cell deriv...
Preprint
BACKGROUND The idea of Artificial Intelligence (AI) has a long history. It turned out, however, that reaching intelligence at human levels is more complicated. Currently we are experiencing a renewed interest in AI, fueled by an enormous increase in computing power and an even larger increase in data in combination with improved AI technologies, li...
Preprint
BACKGROUND The idea of Artificial Intelligence (AI) has a long history. It turned out, however, that reaching intelligence at human levels is more complicated. Currently we are experiencing a renewed interest in AI, fueled by an enormous increase in computing power and an even larger increase in data in combination with improved AI technologies, li...
Article
Full-text available
The use of blood-circulating cell-free DNA (cfDNA) as a "liquid biopsy" in oncology is being explored for its potential as a cancer biomarker. Mitochondria contain their own circular genomic entity (mitochondrial DNA, mtDNA), up to even thousands of copies per cell. The mutation rate of mtDNA is several orders of magnitude higher than that of the n...

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