Advanced dynamic monitoring of cellular status using label-free and non-invasive cell-based sensing technology for the prediction of anticancer drug efficacy

Abstract

Quantitative evaluation of anticancer drug efficacy using in vitro cell-based assays is useful for cancer patients, particularly those who show unconventional cancer development. Nevertheless, conventional chemosensitivity testing often requires widely used labeling agents and time-consuming laboratory procedures that provide low reliability. Label-free non-invasive cell-based assays are desired for dynamic monitoring of cellular status. This critical review first describes conventional chemosensitivity testing and then advanced label-free cell-based technology used to screen anticancer drugs through dynamic monitoring of cellular status, focusing on dosage and the use of drug-resistant cancer cells. Results from label-free cell-based approaches are compared with those of conventional chemosensitivity testing. The cellular statuses, addressed in terms of respective mechanisms and disadvantages, are extracellular fluxes of proton (H(+)), O(2), and anticancer drugs, cell morphology changes, cell-environment interaction, and mitochondrial membrane potential. Finally, a cell-based systems outlook is presented. This paper represents a step toward efficient and accurate initial screening of anticancer drugs and development of compounds and their combined use to achieve pharmacodynamic and pharmacokinetic interactions, and chemotherapy evaluation of particular anticancer drugs for individual patients.

Using label-free screening technology to improve efficiency in drug discovery

“…Current drug-screening efforts recognize the limitations of using biochemical screening assays to represent in vivo effects, particularly with increasing interest in cell biology and system biology-centered approaches [17][18][19][20][21]. Potential 'hits' identified in biochemical screens may fail in in vivo studies, as biochemical assays do not provide a good representative model of native cells and tissues [1,22].…”

One Hour In Vivo-like Phenotypic Screening System for Anti-cancer Drugs Using a High Precision Surface Plasmon Resonance Device

“…A cell-based assay using human cells is frequently employed as a phenotypic assay for chemosensitivity and toxicity tests for anti-cancer drugs. [1][2][3] For this, two-dimensional (2D) cell culture is used often because of its low cost and easy handling. However, 2D cell culture is performed under an altered environment, resulting in the loss of extracellular matrices and three-dimensional (3D) architecture compared to in vivo condition.…”

“…17,19 On the other hand, impedance and electrical current will bring toxicity to live cells and may lead to measurement error. 2 Furthermore, in vivo-like 3D techniques well related to clinical tests requires a long cell culture duration of at least 1 week to endpoint, which necessitates periodical culture medium exchange and may cause low reproducibility brought by human errors. 2 Consequently, many systems including micro fluidics are developed for high throughput phenotypic chemosensitivity testing, 6,12,19 but these are not widely used with high reliability.…”

“…2 Furthermore, in vivo-like 3D techniques well related to clinical tests requires a long cell culture duration of at least 1 week to endpoint, which necessitates periodical culture medium exchange and may cause low reproducibility brought by human errors. 2 Consequently, many systems including micro fluidics are developed for high throughput phenotypic chemosensitivity testing, 6,12,19 but these are not widely used with high reliability. 19,20 To solve these issues, a rapid and reliable in vivo-like phenotypic screening method and device are demanded to give quantitative evaluation at physiological concentrations of drugs.…”

A two-compartment microfluidic device for long-term live cell detection based on surface plasmon resonance

“…[1][2][3] Cellular responses induced by drug stimulations usually persist for a long period. Moreover, the drug action kinetics is meaningful for drug sensitivity tests and personalized cancer treatment.…”