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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 Oncology letters
Vol 21
Issue 3
Date 2021 Mar
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 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
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 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