Acquired drug resistance is one of the major challenges for cancer therapy. There is mounting evidence that cells from the tumour microenvironment have a strong influence in the development of anticancer therapy resistance. Despite the advances of our understanding in cancer, the mechanisms and effects of these tumour associated cells still remains elusive. In addition, there is currently a lack of high-throughput methods suitable for the study of the functional effects of anticancer drugs on tumour samples where the interplay between cancer cells and the tumour microenvironment (TME) is intact.
We have developed an Alginate-based Tissue Engineering (ALTEN) platform, a biomimetic hydrogel system for rapid functional testing of anticancer drugs in explanted tumours. The alginate biomimetic hydrogels allow us to study properties of cancer cells by providing a 3D scaffold that highly resembles the native extacellular matrix (ECM) allowing the permeation of nutrients and gas interchange. Here, we use high-resolution single-cell RNA-seq technologies to analyse the molecular effects of anticancer treatments within the tumour to study the mechanisms of acquired drug resistance.
The combination of ALTEN and scRNAseq technology enable high-throughput and high-resolution screening of tumour explants simultaneously studying the impact of drug therapies in cancer cells and cells from the TME, 1) to establish novel therapeutic combinations, and 2) to characterise the acquisition of drug resistance in standard therapies.
In summary, the ALTEN platform provides an innovative avenue allowing engineering of patient tumour explants to investigate the efficacy of therapies in a high-throughput manner and provide preclinical information on optimising treatments. The integration of both the large-scale drug screening capacity of ALTEN and the high-resolution molecular phenotyping scRNA-seq is set to revolutionise our understanding of the molecular mechanisms of cancer drug resistance.