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establishing and developing co-cultivation systems. These model capable of simulating cell interactions, dynamic
co-culture systems integrate some components of the tumor drug concentrations and drug effects, and angiogenesis or
microenvironment (such as stromal cells and immune mechanical stimulation of cells. 84,85 This advancement will
cells), which will be an important development direction bridge the gap in drug responses observed in in vitro studies
for cancer organoids in the future. 78-83 and real patients and enable a more accurate simulation
of the tumor microenvironment. Different microfluidic
86
Given the limitations of organoids, Organ-on-Chip
is emerging as an innovative platform to optimize cancer organ chips can be connected to each other to construct
a human chip model capable of simulating multi-organ
organoids. Cancer organoids are 3D cell cultures derived interactions. These microphysiological systems can be used
from patient tumors that retain key genetic and histological to study cancer multi-organ metastasis. Shirure et al.
88
87
features of the original cancer. Thus, organoids are self- reported the design of a vascularized tumor chip model
assembling and rely on the extracellular matrix to maintain to simulate physiological material transport at the arterial
the 3D structure. Complex microenvironment interactions end of capillaries within the tumor microenvironment,
and the absence of dynamic fluid flow are significant and demonstrated that the effective delivery of nutrients or
shortcomings of organoids, but they can be addressed with drugs to tumor tissue through the vascular network helps
the organ-on-a-chip technology. By integrating organoids to maintain the physiological activity of tumor organoids
into microfluidic chips, researchers have created “organoid- for a long time. In the organoid model on a vascular chip,
84
on-chip” systems. This system can deliver nutrients and tumor organoids were cultured in a central chamber.
oxygen, demonstrate realistic tumor-stroma interactions, Adjacent chambers were connected to the central chamber,
and improve drug screening platforms to simulate real- and endothelial cells were cultured with fibroblasts in
world pharmacokinetics. The combination of the two hydrogel. It has been demonstrated that perfusion of tumor
85
products, cancer cells and organoid-on-chip, creates organoid cultures with the vascular system can simulate
cancer-on-chips (CoC), which is an advanced tumor angiogenesis 88,89 (Figure 4). Notable features of this vascular
model capable of simulating cell interactions, dynamic tumor chip model include the simulation of dynamic
drug concentrations and drug effects, and angiogenesis or tumor evolution through cell proliferation, angiogenesis,
mechanical stimulation of cells. migration, and intravascular infiltration. 88,89 Therefore,
The combination of the two products, cancer cells, and the integration of the two technologies is expected to
organoid-on-chip, creates CoC, which is an advanced tumor become a new technology for studying the mechanism of

Figure 4. Cancer-on-chip and microfluidic devices. Tumor organoids are cultured in a central chamber. Tumor organoid cultures are perfused with a
vascular system to mimic angiogenesis. Created with BioRender. Cao, K. (2025) https://BioRender.com/12vphvf.

Volume 1 Issue 2 (2025) 9 doi: 10.36922/OR025050008