Abstract
Determination of therapeutic efficacy is a major challenge in developing treatment options for cancer. Prior to in vivo studies, candidate therapeutics are evaluated using cell-based in vitro methods to assess their anti-cancer potential. This review describes the utility and limitations of evaluating therapeutic efficacy using human tumor-derived cell lines. Indicators for therapeutic efficacy using tumor-derived cell lines include cell viability, cell proliferation, colony formation, cytotoxicity, cytostasis, induction of apoptosis, and cell cycle arrest. Cell panel screens, 3D tumor spheroid models, drug-drug/drug-radiation combinatorial analysis, and invasion/migration assays reveal analogous in vitro information. In animal models, cellular assays can assess tumor micro-environment and therapeutic delivery. The utility of tumor-derived cell lines for efficacy determination is manifest in numerous commercially approved drugs that have been applied in clinical management of cancer. Studies reveal most tumor-derived cell lines preserve the genomic signature of the primary tumor source and cell line-based data is highly predictive of subsequent clinical studies. However, cell-based data often disregards natural system components, resulting in cell autonomous outcomes. While 3D cell culture platforms can counter such limitations, they require additional time and cost. Despite the limitations, cell-based methods remain essential in early stages of anti-cancer drug development.
Highlights
Despite advances in technology and medicine, cancer remains one of the most lethal diseases in the world [1]
The methods identified above were originally developed using monolayer cultures. Such systems lack the rich heterogeneity of tumor micro-environments and the corresponding analyses are limited to cell autonomous outcomes that fail to account for impacts on tumor-stromal interaction, angiogenesis and other such factors of a. natural system With greater emphasis on the importance of tumor three-dimensionality (3D) and their corresponding microenvironments with regard to therapeutic efficacy, the advanced stages of the in vitro testing phase often includes 3D cell culture systems to more closely model physiological conditions [82,83,84]. 3D cultures have the added utility of observing characteristics, such as variations in polarity, invasive potential, and matrix independent survival
Tumor-derived cell lines largely preserve the genomic signature of the primary tumors, from which they were sourced [94,95] and data obtained using such cell lines is highly predictive of subsequent clinical outcomes [10,96]
Summary
Despite advances in technology and medicine, cancer remains one of the most lethal diseases in the world [1]. Issues related to cross-contamination celloflines and lack relevance plagued early cell-based [9] It was studies not until[9]. The Center for Molecular Therapeutics 1000 (CMT1000) platform of tumor-derived and cell validated to capture the greatest possible breadth of heterogeneity cancer types. This more lines has been developed and validated to capture the greatest across possible breadth of[10]. Once the sensitivity of certain tumor types has been established for a candidate anti-cancer therapeutic, researchers are able to scale back the breadth of cell types in order to focus their efficacy efficacy cellcell lines, for which the drug the greatest potential.potential. The section below provides an overview of common cell-based assays, which can be used to observe indicators of therapeutic efficacy
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