Bridging the gap between tumor-on-chip and clinics: a systematic review of 15 years of studies

Abstract

We present a multidisciplinary perspective by bringing together physicists, biologists, clinicians, and experts from pharmaceutical companies. We conducted an extensive systematic analysis of publications related to tumor-on-chip.

Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip

“…In conclusion, the last 15 years have witnessed the emerging of ToC platforms as 3D models in oncology, as we recently reviewed. 5 In our hands, ToC are clearly capable to recapitulate the expected cancer death responses upon a variety of anti-cancer treatments, such chemotherapies, 19 targeted therapies, 6 oncolytic viruses, 21 anti-PD-1 (this work), and, even more important, the drug resistance promoted by FAP + CAF-S1 6 , 19 (this work), which has been largely documented by in vivo studies. This evidence supports the biological relevance of the ToC approach and the interest in extending these efforts to the immuno-oncology field 54 (1) to investigate the efficacy of immunotherapy molecules eventually in combination with other drugs, (2) to study the resistance mechanisms, and (3) to potentially provide future predictive tools for personalized medicine in the field of immuno-oncology.…”

“… 2 , 3 , 4 More specifically, ToC technology exploits micro-fabrication and microfluidics to generate cell co-cultures embedded in 3D hydrogels that mimic the extracellular matrix, recapitulating the immune and stromal characteristics of the tumor ecosystem. While the ToC field is exponentially growing, 5 current efforts have mainly relied on established, mostly immortalized cell lines. It is now time to move toward clinically relevant cell models, such as primary autologous cells, and to prepare the ground for translational applications in personalized medicine.…”

“…In this regard, ToC platforms have great potential that is only waiting to be exploited. 3 , 5 For example, we previously showed that a specific immune response, antibody-dependent cell-mediated cytotoxicity, can be recapitulated in a HER2 + breast ToC treated with trastuzumab (Herceptin). 6 Another ToC study revealed a cooperative behavior between cytotoxic T cells in tumor killing.…”

Microphysiological systems as models for immunologically ‘cold’ tumors

“…Less than a handful of ovarian cancer-based micro-fluidic chips incorporates immune cells, however, the TME plays an essential role in tumor initiation, development and therapy response ( Surendran et al, 2021 ; Bouquerel et al, 2023 ). Neutrophils represent a significant portion of cells in the TME ( Swierczak et al, 2015 ; Powell and Huttenlocher, 2016 ), and their abundance has been linked to adverse prognostic outcomes in cancer patients ( Hiramatsu et al, 2018 ; Schiffmann et al, 2019 ; Yin et al, 2019 ; Kim et al, 2022 ).…”

“…Microphysiological systems (MPS), or “organ-on-a-chip” devices, consist of multi-channel systems in the micrometer size range, featuring continuously perfused micro-chambers seeded with cells. In a subset of MPS, the size of the micro-channels is comparable to blood capillaries, which facilitate the transport of nutrients, metabolites and gases, enable the spatiotemporal distribution of signaling molecules and/or cells and provide physiologically relevant biomechanical stimulation in real time to reliably replicate the (patho-) physiological functions of tissues and organs ( Park et al, 2019b ; Baptista et al, 2022 ; Hachey et al, 2023a ; Bouquerel et al, 2023 ). To date, MPS models have been developed for the majority of human tissues and organs, and have also been established to study a diverse range of malignancies, including cancer ( Baptista et al, 2022 ; Hachey et al (2021 ; 2024) ; Jiang et al, 2024 ; Haque et al, 2022 ; Shen et al, 2023 ; Flont et al, 2023 ; Straehla et al, 2022 ).…”