Abstract
Over 90% of potential anti-cancer drug candidates results in translational failures in clinical trials. The main reason for this failure can be attributed to the non-accurate pre-clinical models that are being currently used for drug development and in personalised therapies. To ensure that the assessment of drug efficacy and their mechanism of action have clinical translatability, the complexity of the tumor microenvironment needs to be properly modelled. 3D culture models are emerging as a powerful research tool that recapitulates in vivo characteristics. Technological advancements in this field show promising application in improving drug discovery, pre-clinical validation, and precision medicine. In this review, we discuss the significance of the tumor microenvironment and its impact on therapy success, the current developments of 3D culture, and the opportunities that advancements that in vitro technologies can provide to improve cancer therapeutics.
Highlights
Uncontrolled division of neoplastic cells results in the development of a tumour mass composed of a large variety of cellular and non-cellular components, including the heterogeneous population of cancer cells, infiltrating and resident normal cells, extracellular matrix (ECM) proteins and secreted factors
The complexity within the TME is propagated by the heterogeneous nature of different tumor entities; that is each individual tumor harbors its own unique intricacies comprised of structural, cellular, genetic, and molecular composition
Our continuous effort to improve our understanding of oncology has led to the development of more effective diagnostic and therapeutic approaches
Summary
Uncontrolled division of neoplastic cells results in the development of a tumour mass composed of a large variety of cellular and non-cellular components, including the heterogeneous population of cancer cells, infiltrating and resident normal cells, extracellular matrix (ECM) proteins and secreted factors. Many researchers use 2D cell cultures as the in vitro pre-clinical model for testing anti-tumor drugs before proceeding with in vivo trials [13]. This chip included a layer of endothelium that lined a microvessel wall, the ECM and tumour spheroids to generate a real-time drug delivery model Treatments such as doxorubicin – a standard of care therapy for breast cancer – was loaded in carbon dots to study the penetrance of the treatment through the endothelium to the spheroids, where the efficacy and cytotoxicity of the drug delivery were assessed using in situ assays within the same system [130]. Viable cancer research requires in vitro models that are representative of physiological and pathological conditions, but that can be created quickly and efficiently For this to be possible, we require 3D advanced bioprinting techniques that exploit both intrinsic cell behaviors and innovative biomaterial developments. Synthesis within these areas offers interesting future opportunities for complex 3D model development and the attainment of critical cancer research goals
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