Background: Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit.
Methods: Tumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction.
Results: Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group.
Conclusion: In pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915121 | PMC |
| http://dx.doi.org/10.1038/bjc.2013.753 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CDKN3 as a key regulator of G2M phase in triple-negative breast cancer: Insights from multi-transcriptomic analysis.
IUBMB Life
January 2025
Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
Triple-negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co-expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades.
View Article and Find Full Text PDFOncogenic Human Papillomaviruses Drive One-Third of Sinonasal Squamous Cell Carcinoma and Are Not Mutually Exclusive for Gene Mutations.
Head Neck
January 2025
Departement de Pathologie, Centre Hospitalo-Universitaire Montpellier, Montpellier, France.
Background: The detection rate of oncogenic human papillomaviruses (HPVs) in sinonasal squamous cell carcinomas (SNSCCs) varies among studies. The mutational landscape of SNSCCs remains poorly investigated.
Methods: We investigated the prevalence and prognostic significance of HPV infections based on p16 protein expression, HPV-DNA detection, and E6/E7 mRNA expression using immunohistochemistry, polymerase chain reaction, and in situ hybridization, respectively.
Foliar spray double-stranded RNA targeting HvIAP1 induces high larval and adult mortality in Henosepilachna vigintioctopunctata.
Pest Manag Sci
January 2025
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Background: Exogenous double-stranded RNA (dsRNA) has the potential to serve as an effective alternative to conventional chemical pesticides for the control of insect pests, because it can specifically inhibit essential gene expression in these organisms. However, identifying suitable gene targets remains a crucial step in the development of RNA interference (RNAi)-based pest control strategies.
Results: In this study, three apoptosis-related genes were selected to evaluate their potential for RNAi-induced lethality in Henosepilachna vigintioctopunctata via foliar spray dsRNAs.
Conformational dynamics in specialized CH zinc finger domains enable zinc-responsive gene repression in S. pombe.
Protein Sci
February 2025
Department of Chemistry and Biochemistry, Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
Loz1 is a zinc-responsive transcription factor in fission yeast that maintains cellular zinc homeostasis by repressing the expression of genes required for zinc uptake in high zinc conditions. Previous deletion analysis of Loz1 found a region containing two tandem CH zinc-fingers and an upstream "accessory domain" rich in histidine, lysine, and arginine residues to be sufficient for zinc-dependent DNA binding and gene repression. Here we report unexpected biophysical properties of this pair of seemingly classical CH zinc fingers.
View Article and Find Full Text PDFEdaravone is a Therapeutic Candidate for Doxorubicin-Induced Cardiomyopathy by Activating the Nrf2 Pathway.
Pharmacol Res Perspect
February 2025
Department of Pharmaceutical Health Care and Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Doxorubicin (DOXO) has long been used clinically and remains a key drug in cancer therapy. DOXO-induced cardiomyopathy (DICM) is a chronic and fatal complication that severely limits the use of DOXO. However, there are very few therapeutic agents for DICM, and there is an urgent need to identify those that can be used for a larger number of patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!