Evaluating methods for inducing chemoresistance in colorectal cancer cells: a systematic review protocol with meta-analysis

The in vitro investigation of the antitumor effects of chemotherapeutic agents frequently utilizes immortalized cell lines with chemically induced resistance, either short-term or long-term. However, such studies often lack standardization and display considerable methodological variability, which hinders reproducibility and undermines the reliability of cell viability outcomes. This review protocol aims to systematize methodological data on the in vitro induction of chemoresistance in colorectal cancer (CRC) cell lines and to assess the impact of cell phenotype and induction methodology on the response to treatment with 5-fluorouracil (5-FU). Articles published within the past 10 years and indexed in the MEDLINE, Web of Science, and Embase databases will be included. The review will encompass the development of a search strategy, study selection, data extraction, assessment of methodological quality, and execution of a meta-analysis. Risk of bias will be evaluated using the ToxRTool. Primary variables to be analyzed include: cell phenotype (wild-type or resistant), the method used to generate resistant cells, the induction protocol applied, the selection of culture reagents and inducing agents, and the assessment of cell viability following exposure to 5-FU. The findings of this review may contribute to methodological standardization and improve the reproducibility of cellular resistance assays, while also offering valuable insights into the influence of cellular profiles on the response to the principal chemotherapeutic agent employed in the clinical management of CRC.