Breaking the mold: 3D cell cultures reshaping the future of cancer research

Front Cell Dev Biol. 2024 Nov 26:12:1507388. doi: 10.3389/fcell.2024.1507388. eCollection 2024.

Abstract

Despite extensive efforts to unravel tumor behavior and develop anticancer therapies, most treatments fail when advanced to clinical trials. The main challenge in cancer research has been the absence of predictive cancer models, accurately mimicking the tumoral processes and response to treatments. The tumor microenvironment (TME) shows several human-specific physical and chemical properties, which cannot be fully recapitulated by the conventional 2D cell cultures or the in vivo animal models. These limitations have driven the development of novel in vitro cancer models, that get one step closer to the typical features of in vivo systems while showing better species relevance. This review introduces the main considerations required for developing and exploiting tumor spheroids and organoids as cancer models. We also detailed their applications in drug screening and personalized medicine. Further, we show the transition of these models into novel microfluidic platforms, for improved control over physiological parameters and high-throughput screening. 3D culture models have provided key insights into tumor biology, more closely resembling the in vivo TME and tumor characteristics, while enabling the development of more reliable and precise anticancer therapies.

Keywords: 3D models; chips; drug screening; patient-derived organoids (PDOs); personalized medicine; spheroids.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was co-financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 (10.54499/UIDP/04378/2020) and UIDB/04378/2020 (10.54499/UIDB/04378/2020) of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB, project NANOHEAT (DOI 10.54499/2022.04315.PTDC) and doctoral grants 2021.08629.BD (SC), 2020.07660.BD (BO), 2022.09845.BD (RV), 2020.06599.BD (DF) and 2022.12161.BD (AL).