An organ-on-chip model of lung cancer metastasis for improved patient prognosis

The treatment of tumour growth and dissemination has benefited during the last decades from the implementation of models to monitor the progression of the disease and its response to therapeutic drugs. However, even with the use of such models, tumours inevitably develop resistance and progress, leading to high mortality rates. There is the urgent need of a new generation of in vitro tumor models capable to (i) replicate with higher fidelity the molecular and structural complexity of the tumoral environment, (ii) provide a high-throughput platform where to screen a large battery of anti-cancerous drugs, and (iii) be highly predictive. This new generation of cancer metastasis models may improve our understanding of the mechanistic determinants of cancer metastasis, leading to the development of novel and personalized therapeutic strategies. Organ-on-chip (OC) models of cancer metastasis, or metastasis-on-chip, have emerged as a promising alternative to current in vitro and in vivo tumor models due to their unprecedented capabilities to replicate in a microfluidic chip both the structural and hydrodynamic properties of tumors. Indeed, key events occurring in the metastasis cascade have been investigated using OC models, including angiogenesis, endothelial barrier function, intravasation, extravasation, or organ specificity. Importantly, metastasis-on-chip devices can be combined with biofluids from patients to monitor the personalized response of tumors to anti-cancerous compounds. In this framework, here we show the latest advances in OC to model cancer metastasis and propose, for the first time, the development of a functional lung metastasis-on-chip model. This OC model will replicate all the basic components, functional units, and events occurring during the process of lung cancer metastasis. In a near future, it will allow to (i) relate the mechanical and biochemical factors of the tumor microenvironment with lung cancer expansion, (ii) to study the effect of the lung microcirculation system in tumor dissemination, and (iii) to assess the response of anti-cancerous drugs using samples from cancer patients. Altogether, we anticipate that this new generation of tumor models based on OC technology will provide key insights into the mechano-chemical mechanism of cancer progression, paving the way towards the development of personalized treatments, and univocally, improving cancer patient prognosis.

Acknowledgements

The author acknowledges the Project UID/Multi/50026/2013  (POCI-01-0145-FEDER-007038). This work is also supported by the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement nº 668983 — FoReCaST.