Advanced technological tools to study multidrug resistance in cancer.

The complexity of cancer biology and its clinical manifestation are driven by genetic, epigenetic, transcriptomic, proteomic and metabolomic alterations, supported by genomic instability as well as by environmental conditions and lifestyle factors. Although novel therapeutic modalities are being introduced, efficacious cancer therapy is not achieved due to the frequent emergence of distinct mechanisms of multidrug resistance (MDR). Advanced technologies with the potential to identify and characterize cancer MDR could aid in selecting the most efficacious therapeutic regimens and prevent inappropriate treatments of cancer patients. Herein, we aim to present technological tools that will enhance our ability to surmount drug resistance in cancer in the upcoming decade. Some of these tools are already in practice such as next-generation sequencing. Identification of genes and different types of RNAs contributing to the MDR phenotype, as well as their molecular targets, are of paramount importance for the development of new therapeutic strategies aimed to enhance drug response in resistant tumors. Other techniques known for many decades are in the process of adaptation and improvement to study cancer cells' characteristics and biological behavior including atomic force microscopy (AFM) and live-cell imaging. AFM can monitor in real-time single molecules or molecular complexes as well as structural alterations occurring in cancer cells induced upon treatment with various antitumor agents. Cell tracking methodologies and software tools recently progressed towards quantitative analysis of the spatio-temporal dynamics of heterogeneous cancer cell populations and enabled direct monitoring of cells and their descendants in 3D cultures. Besides, novel 3D systems with the advanced mimicking of the in vivo tumor microenvironment are applicable to study different cancer biology phenotypes, particularly drug-resistant and aggressive ones. They are also suitable for investigating new anticancer treatment modalities. The ultimate goal of using phenotype-driven 3D cultures for the investigation of patient biopsies as the most appropriate in vivo mimicking model, can be achieved in the near future.

Development of an organ-on-chip model for the detection of volatile organic compounds as potential biomarkers of tumour progression.

Early detection of tumours remains a significant challenge due to their invasive nature and the limitations of current monitoring techniques. Liquid biopsies have emerged as a minimally invasive diagnostic approach, wherein volatile organic compounds (VOCs) show potential as compelling candidates. However, distinguishing tumour-specific VOCs is difficult due to the presence of gases from non-tumour tissues and environmental factors. Therefore, it is essential to develop preclinical models that accurately mimic the intricate tumour microenvironment to induce cellular metabolic changes and secretion of tumour-associated VOCs. In this study, a microfluidic device was used to recreate the ischaemic environment within solid tumours for the detection of tumour-derived VOCs. The system represents a significant advance in understanding the role of VOCs as biomarkers for early tumour detection and holds the potential to improve patient prognosis; particularly for inaccessible and rapidly progressing tumours such as glioblastoma. .

The Importance of the Tumor Microenvironment to Understand Tumor Origin, Evolution, and Treatment Response.

During the second half of the twentieth century, oncology adopted a tumor-centric approach to cancer treatment, focusing primarily on the tumor cell to identify new therapeutic targets [...].