Abstract
Epidermal growth factor receptor monoclonal antibody was approved for treatment of metastatic colorectal cancer patients carrying KRAS wild type DNA. However, recent studies showed that patients with KRAS G13D mutation may benefit from EGFR antibody therapy. In this study we tried to explore whether the abundance of KRAS mutation could affect the efficacy of EGFR antibody therapy. We firstly established a PNA-PCR method which could calculate the percentage of KRAS mutation in total DNA and proved its ability on 47 colorectal cancer samples bearing KRAS mutations. Then we analyzed the correlation between the abundance of KRAS mutations and efficacy of EGFR antibody therapy in another 35 metastatic colorectal cancer patients. We proved that PNA-PCR assay could calculate the abundance of KRAS mutation and the percentage of mutant DNA in tumor cells varied a lot (10.8%∼98.3%) on the 47 colorectal cancer patients. The efficacy of EGFR antibody correlated with the abundance of KRAS mutations: in the KRAS mutation less than 30% group, the disease control rate was 44.4% (4/9); the disease control rate of 30∼80% group was 5.6% (1/18) and the >80% group was 12.5% (1/8) (P = 0.038). In summary, our study showed that PNA-PCR method could easily detect the percentage of KRAS mutation in tumor cells and colorectal cancer patients with low abundance of KRAS mutation might benefit from EGFR antibody therapy.
Highlights
Epidermal growth factor receptor (EGFR) monoclonal antibody was approved for treatment of metastatic colorectal cancer patients without KRAS mutations
Validation of PNA-PCR Method on Cell Lines We found that when we added 100 ng KRAS wild-type DNA in the PNA-PCR assay, the PNA could suppress the amplification of wild-type DNA
When we added 100 ng KRAS wild-type DNA and 0.01 ng KRAS mutant DNA in PNA-PCR assay, the KRAS wild-type DNA could be completely and stably suppressed and only KRAS mutant DNA was amplified after confirmation of pyrosequencing (Fig. 1B), which indicated that even the mutant DNA was rare comparing to wild-type, PNA assay still amplify mutant DNA exclusively and this amplification could assist to suppress the wild-type DNA amplification completely
Summary
Epidermal growth factor receptor (EGFR) monoclonal antibody was approved for treatment of metastatic colorectal cancer patients without KRAS mutations. A pooled analysis of three trials showed that specific mutation in KRAS codon 12 had different impact on treatment efficacy in colorectal cancer patients and tumor bearing a KRAS G12D mutation showed a strong trend to a more favorable outcome comparing to other codon 12 mutations [12]. All of these studies showed us that not all KRAS mutant tumors were resistant to anti-EGFR therapy. It was not sufficient to roughly differentiate patients with KRAS mutation status
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
