Research team

Expertise

Translational Cancer Research, particularly involving the study of human material (i.e. blood, tissue and single cells) using high-throughput profiling technologies (next generation sequencing and microarrays), bioinformatics, data integration and systems biology.

Antwerp core facility for bioinformatics (BIOMINA). 01/01/2022 - 31/12/2026

Abstract

High-throughput bio-analytical instruments generate an immense data flow. Translating these data into interpretable insights about the underlying processes of life and disease is increasingly dependent on bioinformatics techniques. Since 2012 BIOMINA (biomedical informatics network Antwerpen) brings together bioinformatics expertise, scattered over life science and computer science labs in our university, in an informal network. With this proposal we wish to transform this network, with its expertise and widely used infrastructure, into a BIOMINA core facility that can deliver a professional bioinformatics service. The mission is to 1) build a sustainable support, training, and collaboration model; 2) increase bioinformatics capacity to meet growing demands; and 3) build a strong bioinformatics community. It is proposed by complementary PIs in the field, to translate the available bioinformatics strengths to support biomedical, clinical, biological, and bioengineering labs within the University and external clients in hospitals and industry.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Chitinase 3-like 1 as novel immunotherapeutic target in triple-negative breast cancer. 01/10/2021 - 30/09/2024

Abstract

Breast cancer is one of the deadliest cancers in women and especially the aggressive subtypes such as triple-negative breast cancer (TNBC) are difficult to treat. Although the immune system provides a natural barrier against invading and metastasizing breast tumor cells, it often fails to halt the disease progression due to immunosuppressive activity orchestrated by breast tumor cells and surrounding stromal cells. The protein chitinase 3-like 1 (CHI3L1) has been highlighted as a potential immunotherapeutic target in cancer due to its stimulation of immunosuppression and metastasis, but its role in breast cancer and more specifically TNBC, remains to be unraveled. This project will investigate the involvement of CHI3L1 signaling in TNBC progression, lymphatic development and dissemination as well as inflammation of triple-negative breast tumors using an in-house characterized immunocompetent intraductal mouse model and clinical samples from TNBC patients. We will also examine the therapeutic effect of CHI3L1 blockade and assess whether such inhibition synergistically enhances the clinical efficacy of immunotherapeutic treatments in TNBC. The results of this project will unequivocally demonstrate if CHI3L1 blockade can be used as an effective TNBC treatment strategy, potentially in combination with other immunotherapies, providing a response to the high clinical demand for better TNBC therapeutics.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Study towards molecular heterogeneity of circulating tumor cells and their representation of metastatic sites in patients with metastatic breast cancer. 01/10/2018 - 30/09/2021

Abstract

Cancer metastases is responsible for 90% of the cancer related deaths. Due to an increased knowledge of the biology of cancer, more patients are referred to targeted therapy. The efficacy of these drugs depends on the molecular characteristics of the cancer cells. In addition, recent research has shown that molecular characteristics of cancer cells can change during cancer progression and metastasis. Since it is practically difficult to sample metastatic tissue repeatedly, investigating alternative matrices is imperative, paving the way for liquid biopsies. One possibility is to evaluate the molecular characteristics of circulating tumor cells, obtained from peripheral blood. However, before these cells can be used as matrix for molecular diagnostics, is should be evaluated if these CTCs have the same characteristics as the primary or metastatic tumor cells. In addition, due to heterogeneity in the primary tumor/metastases, is should be evaluated how many CTCs need to be analyzed in order to capture the dominant driving clones. In order to evaluate this, genomic changes from CTCs will be compared to the genomic composition of the primary tumor and the metastases. If successful, this project will allow a translation of liquid biopsies from the bench to the bedside, sparing patients from difficult and painful treatments.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

The role of infiltrating immune cells in the aggresive phenotype of inflammatory breast cancer and possible new (immuno)therapeutic targets. 01/10/2018 - 30/09/2020

Abstract

IBC is characterized by a rapid onset, redness and swelling of the breast. Despite an aggressive therapy with chemotherapeutics, radiation and surgery the survival rate is the worst among all breast cancers with less than 40 % survival after 5 years. Therefore, further research is necessary. Although IBC and non-IBC (nIBC) tumours are different diseases in many ways, our lab showed that genetically an IBC tumour and a nIBC tumour are not so different after all. Based on these findings we think that the non-cancerous cells that are part of the tumour or the patient's response to the tumour can explain the difference. Thus we are interested in how the surrounding tissue and especially the immune cells respond to IBC and how this is different from nIBC. To examine this we will start our research by determining what types of cells are present in both tumour types and whether they are functioning as they should be. By correlating the presence of certain cell types or functional markers with response to treatment, survival information and properties of the tumour we can see what type of cells or functional markers could predict prognosis or response to therapy and can be called biomarkers. Furthermore, the combination of this information with data about which genes in a tumour sample are over- or underexpressed could lead to a better understanding of the genetic pathways that are important in IBC growth. If we can alter these pathways, we might find new targets for therapy.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Altered TGFβ signaling in the context of a type 2 immune response is a prerequisite for inflammatory breast cancer dissemination and metastasis. 01/01/2017 - 31/12/2017

Abstract

A recent analysis of gene expression microarray data revealed that IBC is characterized by altered TGFbeta and immune signaling. In an independent analysis, we observed that IBC cell motility induced by TGFbeta is remarkably decreased as compared to subtype-matched non-IBC cells. RNA-sequencing demonstrated a particular role for SMAD3, MYC and YY1. Moreover, the roles of SMAD3 and MYC in IBC were confirmed on patient samples using an integrated analysis of gene and protein expression data. YY1 is a powerful transcriptional regulator that is able to repress SMAD3 and activate MYC. In addition, YY1 activity is associated with a type 2 polarized immune response that is characteristic for IBC. Therefore, we hypothesize that the immune response that characterizes IBC leads to YY1 activity, which in turn antagonizes SMAD3 signaling, blunting the TGFbeta response. In turn, a blunted TGFbeta response, leads to patterns of collective migration and formation of tumor emboli, which are typical for IBC. This hypothesis is central to the current research proposal.

Researcher(s)

Research team(s)

    Project type(s)

    • Research Project

    Study towards molecular heterogeneity of circulating tumor cells and their representation of metastatic sites in patients with metastatic breast cancer. 01/10/2016 - 03/04/2019

    Abstract

    Cancer metastases is responsible for 90% of the cancer related deaths. Due to an increased knowledge of the biology of cancer, more patients are referred to targeted therapy. The efficacy of these drugs depends on the molecular characteristics of the cancer cells. In addition, recent research has shown that molecular characteristics of cancer cells can change during cancer progression and metastasis. Since it is practically difficult to sample metastatic tissue repeatedly, investigating alternative matrices is imperative, paving the way for liquid biopsies. One possibility is to evaluate the molecular characteristics of circulating tumor cells, obtained from peripheral blood. However, before these cells can be used as matrix for molecular diagnostics, is should be evaluated if these CTCs have the same characteristics as the primary or metastatic tumor cells. In addition, due to heterogeneity in the primary tumor/metastases, is should be evaluated how many CTCs need to be analyzed in order to capture the dominant driving clones. In order to evaluate this, genomic changes from CTCs will be compared to the genomic composition of the primary tumor and the metastases. If successful, this project will allow a translation of liquid biopsies from the bench to the bedside, sparing patients from difficult and painful treatments.

    Researcher(s)

    Research team(s)

    Project type(s)

    • Research Project

    The role of infiltrating immune cells in the aggresive phenotype of inflammatory breast cancer and possible new (immuno)therapeutic targets. 01/10/2016 - 30/09/2018

    Abstract

    IBC is characterized by a rapid onset, redness and swelling of the breast. Despite an aggressive therapy with chemotherapeutics, radiation and surgery the survival rate is the worst among all breast cancers with less than 40 % survival after 5 years. Therefore, further research is necessary. Although IBC and non-IBC (nIBC) tumours are different diseases in many ways, our lab showed that genetically an IBC tumour and a nIBC tumour are not so different after all. Based on these findings we think that the non-cancerous cells that are part of the tumour or the patient's response to the tumour can explain the difference. Thus we are interested in how the surrounding tissue and especially the immune cells respond to IBC and how this is different from nIBC. To examine this we will start our research by determining what types of cells are present in both tumour types and whether they are functioning as they should be. By correlating the presence of certain cell types or functional markers with response to treatment, survival information and properties of the tumour we can see what type of cells or functional markers could predict prognosis or response to therapy and can be called biomarkers. Furthermore, the combination of this information with data about which genes in a tumour sample are over- or underexpressed could lead to a better understanding of the genetic pathways that are important in IBC growth. If we can alter these pathways, we might find new targets for therapy.

    Researcher(s)

    Research team(s)

      Project type(s)

      • Research Project

      Validation of a preclinical model for breast cancer metastasis and identification of targets for immunotherapy. 01/01/2016 - 31/12/2016

      Abstract

      Despite the discovery of promising targets for breast cancer treatment in preclinical models, the majority of new (immunomodulatory) drugs face inefficiencies and failures in clinical trials. The characterization of more relevant preclinical mouse models for the study of breast cancer growth and metastasis could alleviate this costly problem. Our research group has recently developed and characterized an innovative intraductal mouse model for breast cancer metastasis by injecting luminescent E-cadherin-positive triple-negative 4T1 cells intraductally in the mammary gland of lactating, immunocompetent and syngeneic mice. In the current project we aim to validate this model by comparing it with the classical fat pad model for breast cancer through elegant in vivo imaging techniques that allow visualization of tumor growth, metastasis and lymphatic dissemination. We will also study the immune response and tumor microenvironment in both preclinical models by investigating inflammatory immune cell influx (especially macrophages and neutrophils), analyzing cytokine and chemokine profiles, and performing immunohistochemical evaluation of immune response profiles. This approach will allow the identification of targets for immunotherapy in the biologically relevant intraductal model. The translation to the clinical setting will eventually be established through RNA-sequencing of mastectomized primary tumors from both mouse models and comparing the gene expression profiles with data from samples of breast cancer patients.

      Researcher(s)

      Research team(s)

        Project type(s)

        • Research Project

        Study towards molecular heterogeneity of circulating tumor cells and their representation of metastatic sites in patients with metastatic breast cancer. 01/10/2015 - 30/09/2016

        Abstract

        Cancer metastases is responsible for 90% of the cancer related deaths. Due to an increased knowledge of the biology of cancer, more patients are referred to targeted therapy. The efficacy of these drugs depends on the molecular characteristics of the cancer cells. In addition, recent research has shown that molecular characteristics of cancer cells can change during cancer progression and metastasis. Since it is practically difficult to sample metastatic tissue repeatedly, investigating alternative matrices is imperative, paving the way for liquid biopsies. One possibility is to evaluate the molecular characteristics of circulating tumor cells, obtained from peripheral blood. However, before these cells can be used as matrix for molecular diagnostics, is should be evaluated if these CTCs have the same characteristics as the primary or metastatic tumor cells. In addition, due to heterogeneity in the primary tumor/metastases, is should be evaluated how many CTCs need to be analyzed in order to capture the dominant driving clones. In order to evaluate this, genomic changes from CTCs will be compared to the genomic composition of the primary tumor and the metastases. If successful, this project will allow a translation of liquid biopsies from the bench to the bedside, sparing patients from difficult and painful treatments.

        Researcher(s)

        Research team(s)

          Project type(s)

          • Research Project

          Detection of aberrant androgen receptor transcripts in circulating tumour cells as a predictor of resistance to AR directed treatment in patients with castration resistant prostate cancer. 15/09/2015 - 14/09/2018

          Abstract

          The objective of this study is a multi-center clinical validation of a sensitive assay to detect the presence of wild-type (so-called 'full-length') and alternatively spliced variants (ARV) of the androgen receptor (AR) in enriched circulating tumour cells (CTC) of patients with castration-resistant prostate cancer (CRPC). This approach forms an important tool to predict whether or not a patient with CRPC is likely to benefit from a new line hormonal treatment (including but not restricted to e.g. abiraterone acetate and enzalutamide) and thereby contributes to a more personalized treatment approach for this rapidly increasing patient group.

          Researcher(s)

          Research team(s)

            Project type(s)

            • Research Project

            Growth patterns of liver metastates: from biology to biomarkers. 01/01/2015 - 31/12/2016

            Abstract

            This project aims to characterize liver metastases with a different growth pattern at the molecular level. In a recent study, we showed that these growth patterns are clinically relevant (Frentzas et al, Nat Med, in press). The replacement growth pattern, in which cancer cells replace the normal hepatocytes without disturbing the normal liver architecture, is associated with a more aggressive natural history in addition to a reduced sensitivity to anti-angiogenic drugs. This observation can be explained by the fact that cancer cells that replace normal hepatocytes usurp the sinusoidal vlood vessels in the liver and thus are not dependent of the formation of new blood vessels, which is typical for liver metastases with a desmoplastic growth pattern that are characterized by a tumor nodule surrounded by fibrous tissue. By performing RNA-sequencing, we aim at understanding the biological basis of the different histological growth patterns.

            Researcher(s)

            Research team(s)

              Project type(s)

              • Research Project

              Detection of a potential new biomarker in circulating tumour cells as a predictor of resistance to AR directed treatment in patients with castration-resistant prostate cancer. 01/01/2015 - 31/12/2015

              Abstract

              The objective of this POC study is the assessment of the clinical feasibility and validation of a potential new predictive assay for resistance against androgen receptor (AR)-directed therapies in the treatment of castration-resistant prostate cancer.

              Researcher(s)

              Research team(s)

                Project type(s)

                • Research Project

                Targeted therapy in oncology. 09/09/2014 - 17/03/2015

                Abstract

                This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

                Researcher(s)

                Research team(s)

                  Project type(s)

                  • Research Project

                  Study of the differences in gene expression of angiogenesis-dependent and angiogenesis-independent growth patterns of human tumours using a cDNA microarray technique. 01/10/2002 - 30/09/2003

                  Abstract

                  Histological and biological characteristics of 'non-angiogenic' liver metastases of carcinomas in humans will be studied, also comparing the growth pattern of the primary tumour with that of the metastasis in individual patients. The influence of the growth pattern of liver metastases (angiogenic or non-angiogenic), on the clinical course of the disease will be assessed. A comparison will be made between the medical imaging data (CT and/or MRI) and the different growth patterns. The techniques that will be employed are tissue-micro-arrays in order to determine angiogenic tissue parameters, expression of adhesion molecules and of VEGF, electron microscopy for the study of the ultrastructure of incorporated vessels, RNA-isolation after laser-microdissection and determination of the expression of angiogenesis related genes using real-time RT-PCR. Preparation of a cDNA micorarray experiment.

                  Researcher(s)

                  Research team(s)

                    Project type(s)

                    • Research Project