Abstract

The ideal in vitro recreation of the micro-tumor niche—although much needed for a better understanding of cancer etiology and development of better anticancer therapies—is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.

Highlights

  • Cancer continues to be one of the most important causes of mortality across the globe [1,2,3].Estimates from the World Health Organization (WHO) indicate that cancer is either the first or the second cause of mortality in 91 of 172 countries before 70 years of age

  • The results suggested that this tumor-on-chip device emulated the complex dynamics around the tumor, yielding detailed information about NP transport within a tumor niche

  • This study demonstrated that patient-derived tumor spheroids retain lymphoid and myeloid subsets of immune cells and that those cell populations could be further cultured in microfluidic chips

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Summary

Introduction

Cancer continues to be one of the most important causes of mortality across the globe [1,2,3]. Cancer trends are worrisome, and the number of patients diagnosed with cancer continues to grow In this century, cancer will most probably rank as the single most important hurdle to increasing life expectancy and the main cause of death in every region of the world. Cancer will most probably rank as the single most important hurdle to increasing life expectancy and the main cause of death in every region of the world These numbers impose great pressure on research groups and the pharmaceutical industry to identify more and better drugs that are effective against cancer [4,5,6]. We discuss even more realistic systems where the cancerous tissue is surrounded by both an extracellular matrix and healthy cells and contains vasculature that perfuses nutrients through it

Recapitulation of the niche using tumor-on-chip systems
Tumors-On-Chips: A Superior Alternative for Emulating the Tumor Micro-Niche
Tumor Spheroids
Spheroids in Microfluidic Chambers
Spheroids in a Hydrogel Matrix
Spheroids Surrounded by “Healthy” Tissues
Vascularized Tumor-On-Chip Systems
Applications
Challenges and Perspectives
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