Reference Detail

Ref Type

Journal Article

PMID

(33574948)

Authors

Hasbal-Celikok G, Aksoy-Sagirli P, Altiparmak-Ulbegi G, Can A

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Oncology letters	21	3	2021 Mar	209	Oncol Lett

URL

Abstract Text

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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CTNNB1 S45F	colorectal cancer	resistant	Cetuximab	Preclinical - Cell culture	Actionable	In a preclinical study, a colorectal cancer cell line expressing CTNNB1 S45F was resistant to treatment with Erbitux (cetuximab) in culture (PMID: 33574948).	33574948
CTNNB1 T41A	colorectal cancer	resistant	Cetuximab	Preclinical - Cell culture	Actionable	In a preclinical study, a colorectal cancer cell line expressing CTNNB1 T41A was resistant to treatment with Erbitux (cetuximab) in culture (PMID: 33574948).	33574948
CTNNB1 S33P	colorectal cancer	resistant	Cetuximab	Preclinical - Cell culture	Actionable	In a preclinical study, a colorectal cancer cell line expressing CTNNB1 S33P was resistant to treatment with Erbitux (cetuximab) in culture (PMID: 33574948).	33574948