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Key Event Title
Treatment-resistant gastric cancer
|Level of Biological Organization|
Key Event Components
|regulation of cellular response to drug||occurrence|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Increases in ROS and chronic ROS leading to human treatment-resistant gastric cancer||AdverseOutcome||Shihori Tanabe (send email)||Open for comment. Do not cite||EAGMST Under Review|
|Homo sapiens||Homo sapiens||High||NCBI|
|All life stages||High|
Key Event Description
It is known that diffuse-type gastric cancer, which has a poor prognosis, is treatment-resistant and more malignant compared to intestinal-type gastric cancer (Tanabe et al., 2014). Drug resistance is involved in EMT, which is an important phenomenon exhibiting features similar to cancer stem cells (CSCs) (Du & Shim, 2016).
EMT is involved in metastasis and cancer therapy resistance (Smith & Bhowmick, 2016).
How It Is Measured or Detected
Treatment-resistant gastric cancer and EMT can be detected with biomarkers (Zeisberg & Neilson, 2009).
Treatment-resistant gastric cancer which exhibits EMT phenotype can be detected as the increased level of the transcription factors, zinc finger E-box-binding homeobox 1/2 (ZEB1/2), SNAI1/2, and TWIST2 which are associated with the activation of EMT-related genes (Tanabe et al., 2022a and 2022b).
Domain of Applicability
Drug resistance occurs in Homo sapiens (Du & Shim, 2016).
Regulatory Significance of the Adverse Outcome
Drug resistance is very important in cancer treatment since cancer metastasis and recurrence are some of the main obstacles to treating cancer. Cancer stem cells that share the phenotype of EMT may be targeted in anti-cancer drug development.
Du, B., & Shim, J. S. (2016). Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer. Molecules, 21(7). doi:10.3390/molecules21070965
Smith, B. N., & Bhowmick, N. A. (2016). Role of EMT in Metastasis and Therapy Resistance. J Clin Med, 5(2). doi:10.3390/jcm5020017
Tanabe, S., Aoyagi, K., Yokozaki, H., Sasaki, H. (2014). Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition. International journal of oncology, 44(6), 1955-1970. doi:10.3892/ijo.2014.2387
Tanabe, S., Quader, S., Cabral, H., Ono, R. (2020a). Interplay of EMT and CSC in Cancer and the Potential Therapeutic Strategies. Front Pharmacol, 11, 904. doi:10.3389/fphar.2020.00904
Tanabe S, Quader S, Ono R, Cabral H, Aoyagi K, Hirose A, Yokozaki H., Sasaki, H. (2020b). Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer. Cancers (Basel), 12(12), 3833. doi:10.3390/cancers12123833
Zeisberg, M., & Neilson, E. G. (2009). Biomarkers for epithelial-mesenchymal transitions. J Clin Invest, 119(6), 1429-1437. doi:10.1172/JCI36183