Cancer modeling meets human organoid technology

Science ◽  
2019 ◽  
Vol 364 (6444) ◽  
pp. 952-955 ◽  
Author(s):  
David Tuveson ◽  
Hans Clevers

Organoids are microscopic self-organizing, three-dimensional structures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to create indefinitely expanding organoids starting from tumor tissue of individuals suffering from a range of carcinomas. Alternatively, CRISPR-based gene modification allows the engineering of organoid models of cancer through the introduction of any combination of cancer gene alterations to normal organoids. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting. Here, we review the current state and future prospects of the rapidly evolving tumor organoid field.

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.


2004 ◽  
Vol 10 (4) ◽  
pp. 1263-1273 ◽  
Author(s):  
Zhuo Zhang ◽  
Hui Wang ◽  
Gautam Prasad ◽  
Mao Li ◽  
Dong Yu ◽  
...  
Keyword(s):  

Micromachines ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1122
Author(s):  
Jisoo Kim ◽  
Jinah Jang ◽  
Dong-Woo Cho

The complex and heterogenous nature of cancer contributes to the development of cancer cell drug resistance. The construction of the cancer microenvironment, including the cell–cell interactions and extracellular matrix (ECM), plays a significant role in the development of drug resistance. Traditional animal models used in drug discovery studies have been associated with feasibility issues that limit the recapitulation of human functions; thus, in vitro models have been developed to reconstruct the human cancer system. However, conventional two-dimensional and three-dimensional (3D) in vitro cancer models are limited in their ability to emulate complex cancer microenvironments. Advances in technologies, including bioprinting and cancer microenvironment reconstruction, have demonstrated the potential to overcome some of the limitations of conventional models. This study reviews some representative bioprinted in vitro models used in cancer research, particularly fabrication strategies for modeling and consideration of essential factors needed for the reconstruction of the cancer microenvironment. In addition, we highlight recent studies that applied such models, including application in precision medicine using advanced bioprinting technologies to fabricate biomimetic cancer models. Furthermore, we discuss current challenges in 3D bioprinting and suggest possible strategies to construct in vitro models that better mimic the pathophysiology of the cancer microenvironment for application in clinical settings.


Author(s):  
Qudus Hamid ◽  
Chengyang Wang ◽  
Wei Sun

Micro-Electro-Mechanical Systems (MEMS) technologies have been very attractive and demonstrate the potential for many applications in the field of tissue engineering, regenerative medicine, and life sciences. These fields bring together the multidisciplinary field of engineering and integrated sciences to fabricate three-dimensional models that aides the exploration, generation or regeneration of organic tissues and organs. Presently, monolayer cell cultures are frequently used to investigate potential anti-cancer agents. The issues at hand are that these models give very little in terms of feedback on the effects of the microenvironment on chemotherapeutic and the heterogeneity of the tumor. Three-dimensional tumor and cancer models that mimic the actual disease are developed for in vitro investigations. These models create an environment that enables diseases to have an enhanced evaluation (compared to two dimensional) and eliminate the limitations of the traditional mainstays of cancer research. Three-dimensional Cancer models are economic, allow for biological characterizations. Cancer models are developed from investigations of the actual disease; computer tomography (CT) and magnetic resonance imaging (MRI) allow for biomodeling of the disease’s environmental conditions. Unlike many traditional microfabrication techniques, the Digitial Micro-mirror Microfabrication (DMM) System eliminates the need for mask by incorporating a dynamic mask-less fabrication technique. The DMM is specifically designed for the developments of biologically inspired devices, whether it’s a multicellular spheroid, hollow fiber, or multicellular layer (MCL) models; the DMM has the potential to utilize its dynamic micro mirrors to build the tissue model according to its desired design and characteristics. Each model is specifically designed to mimic the in vivo conditions of the tissue of interest.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A631-A631
Author(s):  
Lino Torres-Dominguez ◽  
Lina Franco ◽  
Mario Abrantes ◽  
Benjamin Walker ◽  
Zachary Tacner ◽  
...  

BackgroundOncolytic Viruses (OV) selectively replicate in and lyse tumor cells and provide stimulation to the immune system. This represents a promising therapeutic option for cancer patients that do not respond well to treatment with immune checkpoint inhibitors. Myxoma virus (MYXV) is a member of the Pox family of double stranded DNA viruses. The natural host of MYXV is a subset of rabbits and hares, but MYXV is able to infect cancer cell lines of humans and other species. The genome of MYXV is relatively large and is amenable to engineering for expression of transgenic proteins making it an excellent oncolytic virus for introduction of immunomodulatory proteins.MethodsThe current work describes the in vitro oncolytic activity and transgene production capability in human cancer cell lines, and in vivo activity of armed myxoma viruses in xenograft human cancer models.ResultsArmed Myxoma viruses demonstrate transgene production and oncolytic activity in multiple human cancer cell lines in vitro and in vivoConclusionsArmed Myxoma viruses present a novel oncolytic viral therapy with ability to modulate immune responses in human cancer modelsEthics ApprovalThis study was approved by OncoMyx Therapeutics and the TD2 IACUC


Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.


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