Modeling human carcinomas: physiologically relevant 3D models to improve anti-cancer drug development

Christine Unger1, Nina Kramer1, Angelika Walzl1

  • 1Institute of Medical Genetics, Medical University of Vienna, Währinger Straße 10, A-1090 Vienna, Austria.

Insights

Developing effective anti-cancer drugs is challenging due to poor predictive preclinical models. This review focuses on advanced 3D cancer models that better mimic human tumors for improved drug response testing.

Area of Science:

  • Oncology
  • Pharmacology
  • Biomedical Engineering

Background:

  • Anti-cancer drug development faces significant inefficiencies, primarily stemming from a lack of efficacy in human patients.
  • High failure rates in clinical trials are often attributed to inadequate preclinical models that fail to accurately predict human responses.
  • Recent advancements have led to the development of improved preclinical cancer models incorporating key features of solid tumors, such as three-dimensionality and heterotypic cell interactions.

Purpose of the Study:

  • To provide an overview of existing in vivo and in vitro cancer models.
  • To highlight models that are three-dimensional (3D) and replicate human tumor-stroma interactions.
  • To focus specifically on models for evaluating anti-cancer drug response.

Main Methods:

  • Literature review of available preclinical cancer models.
  • Inclusion criteria focused on models exhibiting three-dimensionality (3D).
  • Inclusion criteria focused on models that mirror human tumor-stroma interactions.

Main Results:

  • Identification and overview of various 3D in vivo and in vitro cancer models.
  • These models incorporate crucial aspects of solid tumor biology, including spatial organization and cellular heterogeneity.
  • The reviewed models are suitable for assessing anti-cancer drug efficacy by simulating tumor microenvironment conditions.

Conclusions:

  • Improved 3D preclinical models that mimic tumor-stroma interactions are crucial for enhancing anti-cancer drug development.
  • These advanced models offer better prediction of drug response compared to traditional methods.
  • Further development and application of these sophisticated models can help reduce the high failure rates in anti-cancer drug discovery.

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