cancers Review In Vitro Magnetic Techniques for Investigating Cancer Progression Sarah Libring 1,2 , Ángel Enríquez 1,2,3 , Hyowon Lee 1,2,3, * and Luis Solorio 1,4, *   Citation: Libring, S.; Enríquez, Á.; Lee, H.; Solorio, L. In Vitro Magnetic Techniques for Investigating Cancer Progression. Cancers 2021, 13, 4440. https://doi.org/10.3390/cancers 13174440 Academic Editors: Moriaki Kusakabe and Akihiro Kuwahata Received: 30 July 2021 Accepted: 29 August 2021 Published: 3 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; slibring@purdue.edu (S.L.); aenrique@purdue.edu (Á.E.) 2 Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA 3 Center for Implantable Devices, Purdue University, West Lafayette, IN 47907, USA 4 Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA * Correspondence: hwlee@purdue.edu (H.L.); lsolorio@purdue.edu (L.S.) Simple Summary: This review focuses on the advantages achieved by incorporating magnetic forces into culture platforms used to study cancer progression in the laboratory. Due to the complex interactions that occur between cancer cells and their environment throughout primary tumor growth and metastatic spread, benchtop techniques are essential for decoupling these factors at several stages of disease progression where traditional animal models would fail. Breakthroughs in our understanding of cancer biology and mechanics through these benchtop techniques can ultimately lead to better-designed precision medicine platforms and clinical therapeutics for patients. Abstract: Worldwide, there are currently around 18.1 million new cancer cases and 9.6 million cancer deaths yearly. Although cancer diagnosis and treatment has improved greatly in the past several decades, a complete understanding of the complex interactions between cancer cells and the tumor microenvironment during primary tumor growth and metastatic expansion is still lacking. Several aspects of the metastatic cascade require in vitro investigation. This is because in vitro work allows for a reduced number of variables and an ability to gather real-time data of cell responses to precise stimuli, decoupling the complex environment surrounding in vivo experimentation. Breakthroughs in our understanding of cancer biology and mechanics through in vitro assays can lead to better- designed ex vivo precision medicine platforms and clinical therapeutics. Multiple techniques have been developed to imitate cancer cells in their primary or metastatic environments, such as spheroids in suspension, microfluidic systems, 3D bioprinting, and hydrogel embedding. Recently, magnetic- based in vitro platforms have been developed to improve the reproducibility of the cell geometries created, precisely move magnetized cell aggregates or fabricated scaffolding, and incorporate static or dynamic loading into the cell or its culture environment. Here, we will review the latest magnetic techniques utilized in these in vitro environments to improve our understanding of cancer cell interactions throughout the various stages of the metastatic cascade. Keywords: magnetism; cancer; tumor; in vitro; metastatic cascade; review 1. Introduction In 2021, there will be almost 1.9 million newly diagnosed cancer cases and over 600,000 cancer deaths in the United States [1]. Worldwide, there are currently around 18.1 million new cases and 9.6 million cancer deaths yearly [2]. It is clear that advances in the diagnosis and treatment of cancer remain a high priority in biological, healthcare, and engineering research disciplines. Several advances for both cancer treatment and basic research are achieved through the incorporation of magnetic technologies. For example, the untethered transmission of force attainable through magnetic force allows for remote access, facilitates targeted delivery and precise movement in vivo and in vitro, and enables the easy sorting of specific cell types. In this review, we will first give an overview of primary tumor growth and metastatic progression (Section 2) and the principles of magnetic transduction Cancers 2021, 13, 4440. https://doi.org/10.3390/cancers13174440 https://www.mdpi.com/journal/cancers