Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment

  • Authors:
    • Gozde Hasbal‑Celikok
    • Pinar Aksoy‑Sagirli
    • Gulsum Altiparmak‑Ulbegi
    • Ayse Can
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  • Published online on: January 14, 2021     https://doi.org/10.3892/ol.2021.12470
  • Article Number: 209
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Abstract

In anticancer therapy, the effectiveness of therapeutics is limited by mutations causing drug resistance. KRAS mutations are the only determinant for cetuximab resistance in patients with colorectal cancer (CRC). However, cetuximab treatment has not been fully successful in the majority of patients with wild‑type (WT) KRAS. Therefore, it is important to determine new predictive mutations in CRC treatment. In the present study, the association between AKT1/β-catenin (CTNNB1) mutations with the drug resistance to cetuximab and other chemotherapeutics used in the CRC treatment was investigated by using site‑directed mutagenesis, transfection, western blotting and cell proliferation inhibition assay. Cetuximab resistance was higher in the presence of AKT1 E17K, E49K and L52R mutations, as well as CTNNB1 T41A, S45F and S33P mutations compared with that of respective WT proteins. AKT1/CTNNB1 mutations were also associated with oxaliplatin, irinotecan, SN‑38 and 5‑fluorouracil resistance. Furthermore, mutant cell viability in oxaliplatin treatment was more effectively inhibited compared with that of the other chemotherapeutic drugs. In conclusion, AKT1/CTNNB1 mutations may be used as an important predictive biomarker in CRC treatment.
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March-2021
Volume 21 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Hasbal‑Celikok G, Aksoy‑Sagirli P, Altiparmak‑Ulbegi G and Can A: Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment. Oncol Lett 21: 209, 2021
APA
Hasbal‑Celikok, G., Aksoy‑Sagirli, P., Altiparmak‑Ulbegi, G., & Can, A. (2021). Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment. Oncology Letters, 21, 209. https://doi.org/10.3892/ol.2021.12470
MLA
Hasbal‑Celikok, G., Aksoy‑Sagirli, P., Altiparmak‑Ulbegi, G., Can, A."Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment". Oncology Letters 21.3 (2021): 209.
Chicago
Hasbal‑Celikok, G., Aksoy‑Sagirli, P., Altiparmak‑Ulbegi, G., Can, A."Identification of AKT1/β-catenin mutations conferring cetuximab and chemotherapeutic drug resistance in colorectal cancer treatment". Oncology Letters 21, no. 3 (2021): 209. https://doi.org/10.3892/ol.2021.12470