Meet me halfway: Are in vitro 3D cancer models on the way to replace in vivo models for nanomedicine development?

Sabina Pozzi, Anna Scomparin, Sahar Israeli Dangoor, Daniel Rodriguez Ajamil, Paula Ofek, Lena Neufeld, Adva Krivitsky, Daniella Vaskovich-Koubi, Ron Kleiner, Pradip Dey, Shani Koshrovski-Michael, Noa Reisman, Ronit Satchi-Fainaro*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers’ experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer were developed in the last decades. The three dimensions of the tumor, including its cellular and extracellular microenvironment, are recreated by combining co-cultures of cancer and stromal cells in 3D hydrogel-based growth factors-inclusive scaffolds. More complex 3D cultures, containing functional blood vasculature, can integrate in the system external stimuli (e.g. oxygen and nutrient deprivation, cytokines, growth factors) along with drugs, or other therapeutic compounds. In this scenario, cell signaling pathways, metastatic cascade steps, cell differentiation and self-renewal, tumor-microenvironment interactions, and precision and personalized medicine, are among the wide range of biological applications that can be studied. Here, we discuss a broad variety of strategies exploited by scientists to create in vitro 3D cancer models that resemble as much as possible the biology and patho-physiology of in vivo tumors and predict faithfully the treatment outcome.

Original languageEnglish
Article number113760
JournalAdvanced Drug Delivery Reviews
StatePublished - Aug 2021


  • 3D models
  • Drug screening
  • Immunotherapy
  • Tumor-stromal cell interactions
  • hydrogel-based ECM


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