Tumor-on-chip platforms for breast cancer continuum concept modeling.

Our previous article entitled "Proteomics and its applications in breast cancer", proposed a Breast Cancer Continuum Concept (BCCC), including a Breast Cancer Cell Continuum Concept as well as a Breast Cancer Proteomic Continuum Concept. Breast cancer-on-chip (BCoC), breast cancer liquid biopsy-on-chip (BCLBoC), and breast cancer metastasis-on-chip (BCMoC) models successfully recapitulate and reproduce in vitro the principal mechanisms and events involved in BCCC. Thus, BCoC, BCLBoC, and BCMoC platforms allow for multiple cell lines co-cultivation to reproduce BC hallmark features, recapitulating cell proliferation, cell-to-cell communication, BC cell-stromal crosstalk and stromal activation, effects of local microenvironmental conditions on BC progression, invasion/epithelial-mesenchymal transition (EMT)/migration, intravasation, dissemination through blood and lymphatic circulation, extravasation, distant tissues colonization, and immune escape of cancer cells. Moreover, tumor-on-chip platforms are used for studying the efficacy and toxicity of chemotherapeutic drugs/nano-drugs or nutraceuticals. Therefore, the aim of this review is to summarize and analyse the main bio-medical roles of on-chip platforms that can be used as powerful tools to study the metastatic cascade in BC. As future direction, integration of tumor-on-chip platforms and proteomics-based specific approaches can offer important cues about molecular profile of the metastatic cascade, alowing for novel biomarker discovery. Novel microfluidics-based platforms integrating specific proteomic landscape of human milk, urine, and saliva could be useful for early and non-invasive BC detection. Also, risk-on-chip models may improve BC risk assessment and prevention based on the identification of biomarkers of risk. Moreover, multi-organ-on-chip systems integrating patient-derived BC cells and patient-derived scaffolds have a great potential to study BC at integrative level, due to the systemic nature of BC, for personalized and precision medicine. We also emphasized the strengths and weaknesses of BCoC and BCMoC platforms.