Gene expression profiling on pre‐ and post‐erlotinib tumors from patients with head and neck squamous cell carcinoma

Abstract

BackgroundThe purpose of our work was to identify genomic predictive markers of erlotinib response in patients with head and neck squamous cell carcinoma (HNSCC).MethodsTumor tissue biopsies were collected before and after treatment for 39 patients. We analyzed genomic expression of the tumors using microarrays to (1) identify genes differentially expressed in baseline samples in patients who were responders vs nonresponders, (2) characterize erlotinib's effect on gene expression, and (3) identify the pharmacodynamic marker of erlotinib.ResultsGene expression profiles found no statistically significant differentially expressed genes between responders and nonresponders. An exploratory analysis by combining statistical criteria allowed us to identify genes differentially expressed in nonresponders compared to responders and genes whose expression was modified during erlotinib treatment. Finally, the search of pharmacodynamic markers identified cyclin‐dependent kinase 2‐interacting protein (CINP) as a potential marker of erlotinib efficacy because its expression decreased only in patients who were responders to the treatment.ConclusionThis study provides candidate genes potentially involved in erlotinib response in HNSCC. Head Neck, 2012

Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression

“…26,34 Clinical evidence of UGT-associated primary drug resistance The expression of UGT1A has been associated with the response to the epidermal growth factor receptor (EGFR) inhibitor erlotinib in patients with non-small-cell lung cancer (NSCLC) or head and neck cancer. 35,36 Although studies were conducted by using a limited number of patients, the tumour levels of UGT1A mRNA were threefold higher in non-responding patients with head and neck cancer, and those of UGT1A6 mRNA were eightfold higher in nonresponding patients with NSCLC prior to treatment. Consistent with these correlative data, glucuronide conjugation of erlotinib oxidative metabolites is a documented route of its inactivation and elimination, 37 suggesting that elevated levels of UGT reduce sensitivity to erlotinib.…”