Evaluating methods for inducing chemoresistance in colorectal cancer cells: a systematic review protocol with meta-analysis
DOI:
https://doi.org/10.34119/bjhrv8n4-222Keywords:
systematic review, colorectal cancer, chemoresistance, 5-fluorouracil, in vitro modelsAbstract
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.
References
International Agency for Research on Cancer. Colorectal cancer. Feb, 2025. Available at: https://www.iarc.who.int/news-events/iarc-marks-colorectal-cancer-awareness-month-2025/. Accessed at: Aug 5, 2025.
CUI, Weichun; WANG, Yong; SHEN, Xiangji; WU, Xudong; LIU, Hui; XU, Xiuhua. High-expression of LncRNA MAFG-AS1 is associated with the prognostic of patients with colorectal cancer. Rev Assoc Med Bras V. 66 (11): 1530-1535, Nov, 2020.
BILLER, Leah H; DEBORAH, Schrag. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA, V. 325(7): 669-685, Feb, 2021.
BLONDY, Sabrina; DAVID, Valentin David; VERDIER, Mireille; MATHONNET, Muriel; PERRAUD, Aurélie; CHRISTOU, Niki. 5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes. Cancer Sci, V. 111(9): 3142-3154, Sep, 2020.
FRANCIPANE, Maria Giovanna; BULANIN, Denis; LAGASSE, Eric. Establishment and Characterization of 5-Fluorouracil-Resistant Human Colorectal Cancer Stem-Like Cells: Tumor Dynamics under Selection Pressure. Int J Mol Sci, V.20(8):1817, Apr, 2019.
MENEZES, Wliana Lara Moreira; VALENÇA, Diego de Oliveira; FILHO, Antônio Felix da Silva. Reproducibility of in vitro methodologies for colorectal cancer cell proliferation: A literature review. Pesquisas e debates sobre a saúde coletiva: Um intercâmbio entre Brasil e Portugal. Ed. Omnis Sci, 2024.
MCHUGH, Mary L. Interrater reliability: the kappa statistic. Biochemia medica, V. 22, 276-282, 2012.
RINKER, Tyler W, Kurkiewicz D. pacman: Package Management for R. version 0.5.0. Buffalo, New York, 2017.
Wickham, Hadley. ggplot2. Sec Ed. Cham: Springer International Publishing, 2016.
BERG, Kaja C. G.; EIDE, Peter W.; EILERTSEN, Ina A.; JOHANNESSEN, Bjarne; BRUUN, Jarle; DANIELSEN, Stine A.; BJORNSLETT, Merete; MEZA-ZEPEDA, Leonardo A.; EKNAES, Mette; LIND, Guro E.; MYKLEBOST, Ola; SKOTHEIM, Rolf I.; SVEEN, Anita; LOTHE, Ragnhild A. Multi-omics of 34 colorectal cancer cell lines - a resource for biomedical studies. Mol Cancer, V.16, 116, Jul, 2017.
YU, Guili; FAN, Qiangqiang. Deep learning-driven drug response prediction and mechanistic insights in cancer genomics. Sci Rep, V. 15, 20824, Jul, 2025.
HATA, Aaron N Hata; NIEDERST, Matthew J; ARCHIBALD, Hannah L; CARABALLO, Maria Gomez; SIDDIQUI, Faria M; MULVEY, Hillary E; MARUVKA, Yosef E; JI, Fei Ji; BHANG, Hyo-eun C; RADHAKRISHNA, Viveksagar Krishnamurthy; SIRAVEGNA, Giulia; HU, Haichuan; RAOOF, Sana; LOCKERMAN, Elizabeth; KALSY, Anuj; LEE, Dana; KEATING, Celina L; RUDDY, David A; DAMON, Leah J; CRYSTAL, Adam S; COSTA, Carlotta; PIOTROWSKA, Zofia; BARDELLI, Alberto; IAFRATE, Anthony J; SADREYEV, Ruslan I; STEGMEIER, Frank; GETZ, Gad; SEQUIST, Lecia V; FABER, Anthony C; ENGELMAN, Jeffrey A. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med, V. 22(3): 262-9, Mar, 2016.
BERILLA, Erica J. Fratz; ANGART, Phillip; GRAHAM, Ryan J.; POWERS, David N.; MOHAMMAD, Adil; KOHNHOSRST, Casey; FAISON, Talia; YELLELA, Sai Rashmika Velugula; TRUNFIO, Nicholas; AGARABI, Cyrus. Impacts on product quality attributes of monoclonal antibodies produced in CHO cell bioreactor cultures during intentional mycoplasma contamination events. Biotechnol Bioeng, V.117, 2802–2815, Sep, 2020.
RYU, Ann H.; ECKALBAR, Walter L.; KREIMER, Anat; YOSEF, Nir; AHITUV, Nadav. Use antibiotics in cell culture with caution: genome-wide identification of antibiotic-induced changes in gene expression and regulation. Sci Rep, V. 7, 7533, Aug, 2017.
HASSAN, Siti Nazihahasma; AHMAD, Farizan. The relevance of antibiotic supplements in mammalian cell cultures: Towards a paradigm shift. Gulhane Med J, V. 62(4), 224-230, Dec, 2020.
ELLIOT, Robert L.; JIANG, Xian-Peng. The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?”. PLoS ONE, V. 14(4), Apr, 2019.
TEIXEIRA, Nilza Rosa. Cellular mechanisms of resistance to cancer treatment: an integrative literature review. X Fór Rond de Pesq, V. 5 (10), Jan, 2024.
