Tag Archive: Cancer Research

  1. Using Bioprinting to Create Better 3D Tumor Models

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    The generation of relevant 3D in vitro tumor models presents many challenges, but they are increasingly recognized as one of the best preclinical drug-screening platforms and an improved method to study cancer in controlled conditions in the laboratory, due to their enormous potential for recapitulating the appropriate three-dimensional and physiological features of human tumor tissues.

    Traditional methods in which cancer cells are grown in a monolayer in two dimensions result in flat cells where there is no opportunity for cellular contact on all sides. This modifies cellular function due to loss of these interactions, altered cell polarity, and changes in cell shape resulting in a deficient model for understanding cancer biology or establishing appropriate antitumoral therapies. A high number of drugs have been shown to be effective in killing cancer cell monolayers, only to go on to fail in demonstrating any relevance when reaching the clinical stage. However, even though 2D culture models lack realistic complexity, the alternative animal models are very expensive and time consuming and often fail to replicate in vivo human tumor biology. Furthermore, in animal xenografts human cancer cells are usually transplanted to sites in the mouse that are convenient for experimental reasons but unfortunately do not necessarily reflect the original microenvironment of the parent tumor. Thus, 3D in vitro models can be found to be much more realistic than such animal models.

    The main challenge and a priority aspect for relevant in vitro 3D models is the ability to mimic the complexity of the tumor microenvironment appropriately. In order to reproduce the complex interactions between tumor cells, stromal cells and ECM, and replicate the typical tumor compartmentalization in a precise manner, cancer cells would need to be grown in a sphere-shaped organoid, and would have to be combined with biomaterials that allow tunability of both the setup and experimental handling.

    Whilst there are several 3D cell culture techniques available for the generation of tumor spheroids including hanging-drop and non-adherent surface technologies, bioprinting techniques for the generation of tumor spheroids are receiving increasing attention due to their ability to incorporate appropriate tumor architecture in a precise and controlled manner. 3D printing multiple cell types into specific scaffolds can help the generation of improved tumor organoids in which cancer cells are able to self-organize, grow, secrete their extracellular matrix and behave as they would in vivo, thus accurately representing the tumor microenvironment.

    Three-dimensional bioprinting of live human cells has shown that effective in vitro replication of tumor biology is achievable. Several recent articles outline current developments in the use of bioprinted models used in cancer research, opening up a new frontier for the understanding of tumor biology and advancement of cancer therapies.

     

    Image source: Charbe N. et al. 3D bio-printing in oncology research. WJCO, 2017 

     

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    3D In-Vitro Tumor Models Are Changing Cancer Research and Drug Discovery

     

  2. Introducing Biogelx’s new cell biologist, Africa Galvez Flores.

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    Biogelx are happy to welcome on board Africa Galvez Flores, who has just joined the Biogelx team as our resident cell biology researcher. Africa will be working on the development of realistic 3D cancer models using Biogelx proprietary peptide hydrogel technology. These models will be used to test the delivery and effectiveness of bio-orthogonal catalytic systems for the treatment of cancer as part of the Theracat Project.

    Previously, Africa worked on neurodegeneration research at University College London Institute of Neurology and Columbia University Medical Center in New York, studying molecular aspects of neuronal death in cellular models of Parkinson’s and Alzheimer’s. She holds an MSc Neuroscience from University College London and a BSc Biochemistry from the University of Navarra. Nowadays, she is pursuing a scientific career in industry, focused on the usage of innovative approaches to treat disease.

    Africa will be working alongside the rest of the Biogelx team in Biocity, Scotland, and will also be trained on novel cancer therapies in close collaboration with the rest of the Theracat consortium partners. Read more about this fascinating project that we’re just kicking off with Africa, here.

     

    The aim of the THERACAT network is to consolidate Europe as the world leader in novel catalysis-based approach for cancer therapy.

    Theracat Project - Members

     

  3. 3D In-Vitro Tumor Models Are Changing Cancer Research and Drug Discovery

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    Many strategies are used to conduct cancer research and in the development of effective therapies, including analysis of clinical biopsies, in vivo animal models, and in vitro models. In vitro tumor models in three dimensions such as organoids have recently emerged as a promising tool which replicates many features of solid tumors in vivo. The ever-expanding use of organoids is evident by the fact that they were chosen as ‘Method of the Year’ by Nature in 2017.

    Cancer organoids are miniature, three-dimensional cell culture models that allow culturing cancer cells in a spatially relevant manner. Biomimetic hydrogel scaffolds, like those provided by Biogelx, offer the biomechanical and biochemical cues that help to recapitulate the behavior of natural extracellular matrix (ECM) and are essential for regulating cancer cell behavior.

    Extensive experimental evidence has shown that the rigidity of the matrix affects cancer cells growth and activity. Moreover, tissues stiffen during the pathological progression of cancer. However, most of the 3D scaffolds traditionally used, like collagen or Matrigel gels, have the major drawback of presenting very low rigidity, which does not mimic this naturally stiff cancer environment. Furthermore, alternative, newer scaffolds like PEG-based or other synthetic materials don’t have the capacity to mimic sufficiently rigid environments either, and can often only form scaffolds up to 2 kPa. This is not the case with Biogelx materials, which can be formed into gels of stiffness ranging from 0.5 to 100 kPa, hence offering a better option to mimic the stiff ECM of solid tumors. Indeed, such a broad range of stiffness, allows the researcher to model tumors at various stages of disease progression

    Biogelx materials are peptide-based hydrogels which are biochemically tunable as well and provide biomimetic sequences to resemble the tumor matrix in a defined manner. Native ECM molecules (Fibronectins, Laminins, Collagens, etc) are replicated in the gels as functional peptide units that provide cell-to-cell and integrin-binding sites creating a suitable synthetic matrix for reproducible research in cancer biology and drug discovery.

     

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  4. THERACAT: The use of Bio-orthogonal catalysis for cancer therapy

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    Cancer is a major health issue around the globe. The social and economic relevance of this disease is continuously growing. Yearly about 14.1 million people are diagnosed with cancer. Almost 58% of these cases lead to death. To date, the three most established treatments for cancer are surgery, radiotherapy, and chemotherapy. All lead to numerous adverse effects that affect the quality of life of the patient and limit the treatment of the disease. Therefore, the researchers are aiming to find new side-effect-free therapies to treat the most aggressive forms of cancer.

    THERACAT is a scientific consortium, which aims to develop such a new approach to cancer therapy. It is a group, which comprises six academic partners from five different countries and three private sector beneficiaries: TEVA, Tagworks, and Biogelx. Moreover, it consists of three partners active on scientific communication (Cancer Research UK), on management and entrepreneurship (ESADE Business School) and on gender and minorities (UAB-Observatory for Equality). The THERACAT team has established an international programme focused on the development of catalysis-based approaches towards the treatment of cancer.

    THERACAT team - cancer therapy

    The project is based on the idea to deliver nano- and micro-particles bearing a catalytic unit to the tumour site and subsequently, non-active prodrugs are administered to the patient. The prodrugs will be non-toxic and therefore generate limited side effects. Only at the tumour site, the catalytic particles convert the pro-drugs into active anticancer compounds that generate a local and strong effect, as single catalytic species can activate many drug molecules.

    The multidisciplinary researchprogram aims

    • to characterise the bio-orthogonal catalytic materials;
    • to design of novel anti-cancer prodrugs and catalytic strategies for their activation;
    • to develop delivery strategies for the catalytic materials in vitro and in vivo;
    • to evaluate the in vitro and in vivo performances for cancer therapy.

    In addition to evaluating several transition-metal-based catalysts for the activation of selected, chemotherapeutic agents that are currently applied in cancer treatment therapies, the team aims to expand the arsenal of therapeutics that can be activated by bio-orthogonal organometallic catalysts and to develop novel spectroscopy and microscopy methods that will enable to test the prodrug activating capacity of the nanomaterials proposed in THERACAT. In later stages of the project, the pairs of catalytic materials and prodrugs developed will be evaluated and studied extensively in in vitrobiological models as well as orthotopic cancer models in mice to determine the biodistribution of the newly synthesized compounds and the anticancer activity of the activated prodrugs in vivo. A key part of the project will be the development of 3D hydrogel-based cancer models at Biogelx.

     

    THERACAT is a Horizon2020 funded Marie Skłodowska-Curie European Training Network (H2020-MSCA-ITN-2017, Project 765497). This multidisciplinary programme will train 13 early stage researchers, with the combination of research expertise, cutting-edge facilities, and the complementary skills present in the consortium providing a great platform for the advancement of their careers, as well as of the knowledge of catalysis-based anticancer therapies. Stay connected with www.biogelx.com/blog for more updates on the project!

     

    THERACAT members: Fundació Institut de Bioenginyeria de Catalunya | Rijksuniversiteit Groningen | Technische Universiteit Eindhoven | Universitat Basel, University of Edinburgh | Tel Aviv University | Cancer Research UK | Fundación ESADE | Universitat Autònoma de Barcelona | TEVA Pharmaceutical Industries Ltd. | Tagworks | Biogelx Limited.