Using 3D Tumoroid Models for Cancer Research

Advances and Applications of Tumor-on-a-chip Technology Tumor-on-a-chip technology has developed rapidly, providing an innovative platform for high-precision simulation of tumor microenvironments. Key advances include the combination of 3D cell culture, microfluidic systems, and advanced biomaterials, which enhance the physiological relevance and functionality of these models. (1) Advances: ·      3D cell culture: More accurately simulates the complex structure of tumors than traditional 2D culture. ·      Microfluidics: Controls the microenvironment by precisely regulating nutrient flow, waste removal, and drug delivery, replicating dynamic conditions in the human body. ·      Advanced biomaterials: Uses biocompatible and tunable materials to create scaffolds that closely resemble the extracellular matrix, supporting realistic cell behavior. (2) Applications: ·      Drug screening and development: Tumor-on-a-chip models enable high-throughput screening of anticancer drugs, which can more accurately predict drug efficacy and toxicity than traditional methods. ·      Personalized medicine: By using patient-derived cells, these devices can simulate individual tumors, allowing for testing of personalized treatment options and optimizing treatment strategies. ·      Cancer biology research: Facilitates research on tumor growth, metastasis, and the interaction between cancer cells and their microenvironment, deepening our understanding of cancer mechanisms. ·      Immunotherapy Testing: Providing a platform to evaluate the efficacy and safety of novel immunotherapies, including checkpoint inhibitors and CAR-T cells, in a controlled, human-relevant setting. Overall, tumor-on-a-chip technology continues to evolve, offering a promising avenue for improving cancer research, drug development, and personalized treatment, ultimately aiming to improve patient outcomes. Reference [1] Xingxing Liu et al., Microsystems & Nanoengineering 2021 (https://lnkd.in/ezSe5F2V)

A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine. https://lnkd.in/ezS_NNHj

Colorectal Cancer: University of Geneva team has developed a new approach to customize treatments by testing on organoids. Published: 04 April 2023. Excerpt: With more than 1.4 million people affected each year - 700,000 fatally- colorectal cancer is third most diagnosed cancer in the world and second most deadly, after lung cancer. Treatment is based primarily on combination of chemotherapies called FOLFOXIRI. Effectiveness varies from patient to patient and side effects are significant. It also leads to progressive drug resistance in most patients. How can combination chemotherapy be tested and optimized for each patient without causing numerous side effects? A UNIGE team led by Patrycja Nowak-Sliwinska, associate professor School of Pharmaceutical Sciences at the Faculty of Science of the UNIGE, and a member of Translational Research Centre in Oncohematology (CRTOH), has found the solution by using organoids. These three-dimensional cellular structures, created in the lab, reproduce structure and functions of certain tissues and organs. "The micro-tissues are not organs,’’ explains George M. Ramzy, a postdoc researcher in the School of Pharmaceutical Sciences at UNIGE and first author of the study. ‘‘They have some important physiological differences, such as not having vascular or nervous systems. However, they are very effective models for testing treatments.’’ Researchers started with cancer tissue from untreated patients at Geneva University Hospitals (HUG). By cultivating stem cells from tissues - which gradually divided and organized into three-dimensional structures - scientists were able to produce #organoids, or tumoroids, from each patient’s tumor. ‘‘We tested different drugs on the models, without knowing their genetic background,’’ explains Patrycja Nowak-Sliwinska. This individual background largely determines effectiveness of treatments. Researchers based their entire study on observation of cells’ response in real time. Collaboration between UNIGE research lab and EPFL, researchers were able to determine the stage of each patient’s tumor and main mutations involved in disease progression. This information is essential to better understand choice and mechanism of action of each drug combination. ‘‘Each patient is different and requires a specific treatment,’’ adds Patrycja Nowak-Sliwinska. This innovative approach, without animal models was just #patented. It offers personalized treatment for many forms of cancer, but also for other diseases such as cardiovascular or viral diseases. #Trials are underway for #renal #cancer. For the research team, the next step will be to work on organoids from pre-treated colon cancer tumors, which show signs of resistance. The aim will also be to shorten duration of the optimization process. Research Published: Journal of Experimental & Clinical Cancer Research DOI: 10.1186/s13046-023-02650-z https://lnkd.in/eATRsHTD