pp 1-33 | Cite as

Organotypic Models in Drug Development “Tumor Models and Cancer Systems Biology for the Investigation of Anticancer Drugs and Resistance Development”

  • Érica Aparecida de Oliveira
  • Colin R. Goding
  • Silvya Stuchi Maria-EnglerEmail author
Part of the Handbook of Experimental Pharmacology book series


The landscape of cancer treatment has improved over the past decades, aiming to reduce systemic toxicity and enhance compatibility with the quality of life of the patient. However, at the therapeutic level, metastatic cancer remains hugely challenging, based on the almost inevitable emergence of therapy resistance. A small subpopulation of cells able to survive drug treatment termed the minimal residual disease may either harbor resistance-associated mutations or be phenotypically resistant, allowing them to regrow and become the dominant population in the therapy-resistant tumor. Characterization of the profile of minimal residual disease represents the key to the identification of resistance drivers that underpin cancer evolution. Therapeutic regimens must, therefore, be dynamic and tailored to take into account the emergence of resistance as tumors evolve within a complex microenvironment in vivo. This requires the adoption of new technologies based on the culture of cancer cells in ways that more accurately reflect the intratumor microenvironment, and their analysis using omics and system-based technologies to enable a new era in the diagnostics, classification, and treatment of many cancer types by applying the concept “from the cell plate to the patient.” In this chapter, we will present and discuss 3D model building and use, and provide comprehensive information on new genomic techniques that are increasing our understanding of drug action and the emergence of resistance.


2D- and 3D-culture models Cancer drug resistance Cancer system biology Drug-testing platform 



Two-dimensional space


Three-dimensional space


Abelson murine leukemia viral oncogene homolog 1


Apurinic/apyrimidinic endonuclease 1


The breakpoint cluster region protein


v-Raf murine sarcoma viral oncogene homolog B


BRAF inhibitor


Breast cancer gene


Cancer-associated fibroblasts


Cancer drug resistance database


Cancer Cell Line Encyclopedia


Chromatin immunoprecipitation sequencing


Chronic myeloid leukemia


Clustered regularly interspaced short palindromic repeats


Cancer stem cells


The Cancer Therapeutics Response Portal


Deoxyribonucleic acid


DNA sequencing


Endothelial cells


Extracellular matrix


Epidermal growth factor receptor


Food and Drug Administration


Genomics of Drug Sensitivity in Cancer


Gene Expression Omnibus


Human epidermal growth factor receptor-type 2


Human lung fibroblast cell line


Hedgehog signaling pathway


Human dermal blood microvascular endothelial cxells


The half maximal inhibitory concentration


International Cancer Genomics Consortium




Lemur tyrosine kinase 3


Long non-coding RNA


Mitogen-activated protein kinase kinase


Small non-coding RNA molecule


Gold and magnetic iron oxide


MicroRNA sequencing


Microphthalmia-associated transcription factor


Matrix metallopeptidase


Mesenchymal stem cells


Multiple omics


National Center for Biotechnology Information


National Institute of Health


National Library of Medicine


Neuroblastoma RAS viral oncogene


Tumor protein p53


Phospho-5′ adenosine monophosphate-activated protein kinase


Human pancreatic cancer cell line


Prostate apoptosis response 4


Poly ADP-ribose polymerase


Non-small cell lung cancer


Polymerase chain reaction


Porous polydimethylsiloxane


Patient-derived organoids


Phospho-extracellular signal-regulated kinase


Pyruvate kinase isozymes M1/M2


Ribonucleic acid


RNA sequencing


Reverse-phase protein array


Physiological stem cells


Single-cell RNA sequencing


Secreted frizzled-related protein 2


Single nucleotide polymorphisms


Human non-small cell lung cancer cell line


Transcription activator-like effector nuclease


Tumor-associated macrophages


The Cancer Genome Atlas


Tyrosine kinase inhibitors


United Kingdom


United States of America


Wingless-related integration site


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Érica Aparecida de Oliveira
    • 1
  • Colin R. Goding
    • 2
  • Silvya Stuchi Maria-Engler
    • 1
    Email author
  1. 1.Skin Biology and Melanoma Lab, Department of Clinical Chemistry and Toxicology, School of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil
  2. 2.Ludwig Institute for Cancer Research, Nuffield Department of Clinical MedicineUniversity of OxfordOxfordUK

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