Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR)

Abstract

MicroRNAs were described to target mRNA and regulate the transcription of genes involved in processes de-regulated in tumorigenesis, such as proliferation, differentiation and survival. In particular, the miRNA let-7 has been suggested to regulate the expression of the KRAS gene, a common mutated gene in non-small cell lung cancer (NSCLC), through a let-7 complementary site (LCS) in 3′UTR of KRAS mRNA. We have reported the analysis performed on the role of the polymorphism located in the KRAS-LCS (rs61764370) which is involved in the disruption of the let-7 complementary site in NSCLC patients enrolled within the TAILOR trial, a randomised trial comparing erlotinib versus docetaxel in second line treatment. In our cohort of patients, KRAS-LCS6 polymorphism did not have any impact on both overall survival (OS) and progression free survival (PFS) and was not associated with any patient’s baseline characteristics included in the study. Overall, patients had a better prognosis when treated with docetaxel instead of erlotinib for both OS and PFS. Considering KRAS-LCS6 status, the TG/GG patients had a benefit from docetaxel treatment (HR(docetaxel vs erlotinib) = 0.35, 95% CI 0.15–0.79, p = 0.011) compared with the TT patients (HR(docetaxel vs erlotinib) = 0.72, 95% CI 0.52–1.01, p = 0.056) in terms of PFS.

Genetic Association of Drug Response to Erlotinib in Chinese Advanced Non-small Cell Lung Cancer Patients

“…EGFR-TKI treatment for NSCLC have an impressive profile of therapeutic responses and ADR compared with standard chemotherapies. Previous studies showed relationships between both somatic activating mutations in EGFR coding sequences and SNP of drug metabolism genes with therapeutic responses to EGFR-TKI (Ganzinelli et al, 2015 ; Lópezayllón et al, 2015 ; Ruan et al, 2016 ). For example, rs884225 in EGFR is associated with erlotinib-induced ADR.…”

DNA Repair Gene Polymorphisms in Non-Small-Cell Lung Cancer Patients Treated with First-Line Platinum-Containing Chemotherapy

“…The rs11615, rs3212986, rs17655, and rs1047768 SNPs were genotyped using MGB probes specifically designed for Allelic Discrimination and TaqMan SNP Genotyping assay (Applied Biosystems, Monza, Milan), based on real-time PCR technique (ABI 7900, Applied Biosystems). Polymerase chain reaction was performed in 384-well plates, as previously described in detail (34, 35). Allelic Discrimination Sequence Detection Software (Applied Biosystems) was used for the analysis.…”

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma

“…In the last decade, many studies have been published analyzing the prognostic and predictive roles of KRAS SNPs rs10771184 and rs61764370 in miRNA binding sites of the KRAS gene. And while several studies emphasized the potential role of these SNPs as molecular biomarkers in various tumors for disease susceptibility [56,57], prognosis [18,58], survival [59,60], and prediction of drug response [61], others found no correlation [62,63]. However, to the best of our knowledge, we are the first study to publish an association between these two polymorphisms and KRAS protein expression.…”