High ERCC1 Levels Research Articles

ERCC1 Overexpression Increases Radioresistance in Colorectal Cancer Cells.

Simple SummaryThe 20–30% of locally advanced rectal cancer patients undergoing preoperative concurrent chemoradiotherapy had no expected efficacy, and ERCC1 overexpression was found in these tumor tissue patients. In the interest of confirming and adding details to our understanding of that correlation, The Tet-on gene expression system was used to examine ERCC1 functionality and stability. Our data from regulatable HCT116-Tet-on and COLO205-Tet-on cell lines verified the increased radioresistance in colorectal cancer cells that are associated with ERCC1 overexpression, and they confirmed a high correlation between ERCC1 levels and radiotherapeutic efficiency. Furthermore, overexpression of ERCC1 also increases cell migration under radiation exposure. Additional data from ERCC1 expression regulation in vivo confirmed that the overexpression of increased cancer radiation resistance suggests that ERCC1 expression plays a key role.Preoperative concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced rectal cancer patients, but 20–30% do not benefit from the desired therapeutic effects. Previous reports indicate that high levels of ERCC1 reduce the effectiveness of cisplatin-based CCRT; however, it remains unclear as to whether ERCC1 overexpression increases radiation resistance. To clarify the correlation between ERCC1 levels and radiation (RT) resistance, we established two cell lines (HCT116-Tet-on and COLO205-Tet-on), induced them to overexpress ERCC1, detected cell survival following exposure to radiation, established HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models, and detected tumor volume following exposure to radiation. We found that ERCC1 overexpression increased radiation resistance. After regulating ERCC1 levels and radiation exposure to verify the correlation, we noted that increased radiation resistance was dependent on ERCC1 upregulation in both cell lines. For further verification, we exposed HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models to radiation and observed that ERCC1 overexpression increased colorectal cancer tumor radioresistance in both. Combined, our results suggest that ERCC1 overexpression may serve as a suitable CCRT prognostic marker for colorectal cancer patients.

1139P - Sensitizing HRAS overexpressing head and neck squamous cell carcinoma (HNSCC) to chemotherapy

BackgroundHRAS is mutated or overexpressed in various cancers. Although numerous studies have demonstrated that HRAS mutations (HRASmut) promote chemoresistance in HNSCC, the effect of wild type HRAS overexpression (wtHRASov) on chemotherapy has not yet been studied. We sought: i. to investigate the repair capacity of wtHRASov tumors in cisplatin- induced damage and ii. to explore the cisplatin sensitizing effect of HRAS inhibitor tipifarnib. MethodsMutation/RNA and cisplatin IC50 data were retrieved from the Cancer Genome Atlas (TCGA) and COSMIC Cell Lines Project respectively. Modified Z-score was used to define HRAS overexpression. Patient derived xenografts (PDXs) were generated from treatment naïve HNSCC patients. Mutational and expression profile of tumor grafts was identified by whole exome sequencing, IHC, qRT-PCR and western blot analysis. Cisplatin or cisplatin combined with tipifarnib was used for PDX’s treatment. Therapy response was monitored by sequential tumor volume measurements over time. ResultsOur analysis of available RNA and cisplatin IC50 data from HNSCC cell lines demonstrated that wild type HRAS levels are positively correlated with cisplatin resistance. To identify resistance signatures in wtHRASov tumors, we compared the TCGA HNSCC transcriptomes of HRAS-altered (HRASmut or wtHRASov) and HRAS- unaltered tumors. Approximately 6% of HNSCCs were overexpressing HRAS, and there was only partial overlap with the 6% of HRASmut tumors. Moreover, ERCC1 was found highly upregulated in HRAS altered group and especially among wtHRASov subcluster. To further study the resistance of wtHRASov tumors, we generated a cohort of HNSCC PDXs and acquired their mutational, expression and chemosensitivity profile. PDX tumors harboring a profile similar to wtHRASov TCGA cluster exhibited a strong chemoresistant squamous phenotype associated with high ERCC1 levels. Interestingly, these tumors were resensitized to cisplatin when subjected to cisplatin/tipifarnib combinatorial treatment. ConclusionsERCC1 expression is a well-established biomarker for cisplatin resistance. Our study demonstrates that wtHRASov tumours represent a distinctive entity that strongly express ERCC1 and can be resensitized to cisplatin by tipifarnib. Legal entity responsible for the studyThe authors. FundingKura Oncology. DisclosureT. Rampias: Research grant / Funding (institution): Kura Oncology Company. All other authors have declared no conflicts of interest.

A randomized phase II pilot study prospectively evaluating treatment for patients based on ERCC1 for advanced/ metastatic esophageal, gastric, or gastroesophageal junction cancer: SWOG S1201.

4009 Background: Platinum based treatment (tx) is standard in HER2 negative patients (pts) with advanced esophagogastric cancer (AEGC). Retrospective data suggest intratumoral ERCC1 levels may determine platinum sensitivity. A randomized phase II study was performed in pts with AEGC to explore whether the efficacy of a platinum 5-FU/LV/Oxaliplatin (FOLFOX) vs. non-platinum containing regimen irinotecan/taxotere (IT) differed according to ERCC1 levels. Methods: 203 untreated pts with AEGC, Her2 -, Zubrod PS 0-1, were randomized to FOLFOX vs. IT, stratified by intratumoral ERCC1 low (<1.7) vs. high (≥1.7). Objectives were to assess PFS and OS in all pts treated with FOLFOX compared with IT, and in those pts with low and high ERCC1 levels and to assess for interactive effects between ERCC1 expression and tx arm. Results: 86% of pts had ERCC1 values <1.7. Thus, evaluation of ERCC1 pts in the high subgroup was not feasible. Tx groups were well matched by age, sex, race, ERCC1 level, and site. A series of K-M plots were used to explore whether tx arm differences in PFS varied based on ERCC1 levels; little evidence of such was noted. Grade ≥ 3 anemia, dehydration, diarrhea and fatigue were greater in pts with IT. Grade ≥ 3 neuropathy and decreased neutrophils were greater in pts with FOLFOX. Conclusions: In all pts, FOLFOX had a statistically superior PFS and RR, when compared with IT. In pts with ERCC1 <1.7 receiving FOLFOX, PFS and RR was statistically superior, with no difference in OS. There was no significant evidence of differential treatment effect on PFS across ERCC1 levels. Clinical trial information: NCT01498289. [Table: see text]

Chemosensitizing effect of shRNA-mediated ERCC1 silencing on a Xuanwei lung adenocarcinoma cell line and its clinical significance

Lung cancer is a common fatal malignancy in both men and women. Xuanwei, Yunnan has the highest incidence of lung cancer in China. The area has a specific risk factor in the domestic combustion of bituminous coal, and lung cancer patients from this area tend to be resistant to platinum-based treatments. However, little is known about the mechanism of platinum resistance in patients from Xuanwei. Herein, we used lentiviral infection with shRNA to silence expression of the DNA repair enzyme ERCC1 in XWLC05 both in its RNA and protein expression level, a lung adenoma cell line derived from a patient from Xuanwei. ERCC1 expression in this cell line is high and contributes to its resistance to cisplatin. Suppression of ERCC1 decreased XWLC05 proliferation in vitro (IC50 of cisplatin 1.34 µM for shRNA-infected cells vs. 4.54 µM for control cells) and increased the apoptotic rate after treatment with cisplatin (81.2% shRNA cells vs. 58% control cells, P<0.05). Progression-free survival was longer in ERCC1-negative lung adenoma patients than those with high ERCC1 levels (30 vs. 11 months, P<0.0001). ERCC1 expression was identified as a prognostic marker for overall survival in the patient cohort with operable lesions. Taken together, our data identify ERCC1 as a disease marker in lung adenoma patients from Xuanwei and confirm the significance of resection for the subsequent effect of platinum treatment in these patients. Additional studies are needed to determine the mechanism of ERCC1-induced platinum resistance in lung adenoma patients from Xuanwei.

Outcomes of ERCC1 high locally advanced esophageal cancer patients treated with non-platinum vs platinum based CRT.

192 Background: ERCC1 is a DNA excision repair enzyme which repairs the DNA adduct damage caused by platinum and hence high levels of ERCC1 has been associated with platinum resistance. Thus utility of platinum as a first line chemotherapy in esophageal cancers with high ERCC1 levels is controversial. SWOG S0356 trial noted a significantly low 2 year overall survival of 37% for platinum based CRT in ERCC1 high esophageal carcinomas, yet no studies have identified the alternative first line chemotherapy. Our Program utilized combined irinotecan 65mg/m2 on D1 and D8 and nab-paclitaxel 100mg/m2with concurrent radiation therapy of 50.4Gy for ERCC1 high esophageal cancers at the treating physician’s discretion. We compared the differences in survival with non-platinum versus platinum CRT. Methods: Retrospective analysis from 2011 to 2016 identified 25 locally advanced esophageal cancer patients in whom ERCC1 levels were checked. Out of this 25 patients 23 had high ERCC1 levels and 2 had low ERCC1 levels. Patients with low ERCC1 were excluded. Patients with high ERCC1 levels received either non-platinum or platinum CRT as neo-adjuvant, adjuvant or definitive chemotherapy. Results: Patient characteristics: Male 69.5%, female 30.5%, squamous 43.4%, adenocarcinoma 52.1%, other 4.5%, operable 39%, non-operable 61%. Non-platinum therapy was utilized for 69.5% and platinum based therapy for 30.5% of the patients. Kaplan-Meier analysis for survival showed clear separation of the curves around 2 years. Median overall survival of non-platinum doublet was not reached during a median follow up of 22 months. Overall survival at 2 years was 57%. The median overall survival for the platinum doublet was 22 months and the 2 year overall survival was 42%. (p = 0.22). Hazard ratio (HR) 0.48(95% CI 0.14-1.58 p = 0.23) .This statistical non significance was due to small sample size. Conclusions: Abraxane and irinotecan showed improved overall survival in the ERCC1 high group when compared with platinum based therapy demonstrated both in our population and the SWOG 0356 trial. [Table: see text]

The role of pharmacogenetics in the new ESMO colorectal cancer guidelines.

The role of pharmacogenetics in the new ESMO colorectal cancer guidelines.

MAVERICC, a phase 2 study of mFOLFOX6-bevacizumab (BV) vs FOLFIRI-BV with biomarker stratification as first-line (1L) chemotherapy (CT) in patients (pts) with metastatic colorectal cancer (mCRC).

493 Background: Standard 1L mCRC treatment (tx) includes a CT backbone (e.g., modified leucovorin [LV]/5-fluorouracil [5-FU]/oxaliplatin [mFOLFOX6] or LV/ 5-FU/ irinotecan [FOLFIRI]) and biologic therapy (e.g., BV). The preferred CT backbone for anti VEGF tx is unknown. MAVERICC (NCT01374425), a global, randomized, open-label, phase 2 trial, assessed tx efficacy and safety of mFOLFOX6-BV vs FOLFIRI-BV in pts with mCRC. Intratumoral ERCC1 and plasma VEGF-A were studied as biomarkers for oxaliplatin- and BV-containing tx, respectively. Methods: Pts with mCRC (≥1 measurable metastatic lesion, ECOG performance status ≤1) were randomized 1:1 to receive BV (5 mg/kg) + mFOLFOX6 or FOLFIRI every 2 weeks, stratified by ERCC1 level (low [£1.7] vs high [&gt;1.7]) and region. VEGF-A levels were measured at baseline. Primary objectives were to evaluate: ERCC1 as a biomarker of progression-free survival (PFS) in 1L mCRC tx (mFOLFOX-BV vs FOLFIRI); and VEGF-A as a biomarker for BV and as a biomarker in combination with ERCC1 for PFS following CT + BV. Secondary objectives were to evaluate: the effect of ERCC1 and VEGF-A on overall survival (OS), objective response rate, hepatic metastases resection, and safety. PFS and OS were estimated by Kaplan–Meier methods, hazard ratios (HR) were estimated by Cox regression, and p-values were based on stratified log-rank tests. ERCC1 biomarker analyses are presented here. Results: A total of 376 pts were randomized: median age, 61 yr; white race, 83%; US region, 85%. Baseline characteristics: ERCC1 high, 35%; KRAS mutant, 34%. Efficacy results are shown (see Table). Conclusion: Consistent with previous findings, PFS and OS were comparable in pts treated with either 1L mFOLFOX6-BV or FOLFIRI-BV. Exploratory analyses within pts with high ERCC1 levels suggest consistent results. VEGF-A analyses are ongoing. Clinical trial information: NCT01374425. [Table: see text] [Table: see text]

ERCC1 mRNA levels as a useful prognostic biomarker for extrahepatic cholangiocarcinoma with R0 resection.

239 Background: To date, no prognostic biomarker for biliary tract carcinoma has been identified. In previous studies of biliary tract carcinoma, no reliable data was found due to the varying composition of the cancer type (gallbladder, cholangiocarcinoma, and ampullary carcinoma), differences in tumor location, a mixture of curative and non-curative operations, and differences in operative methods. Methods: Fifty extrahepatic cholangiocarcinoma patients who underwent a pancreatoduodenectomy with R0 resection at the Tokyo Women’s Medical University Hospital were examined. All patients were pathologically diagnosed as having papillary or tubular adenocarcinoma. T-RNA was extracted from FFPE samples, and mRNA expression levels were measured by real-time RT-PCR. Results: In the preliminary analysis, 10 patients who have survived more than 5 years (LS group) and 10 patients who had a relapse within 2 years (SS group) were selected. EGFR, AREG, EREG, MMP-9, CDH-1, PARP1, and ERCC1 mRNA expression were examined; only the ERCC1 mRNA levels showed a significant difference between the LS and SS groups (median ERCC1: LS 26.5 vs. SS 9.7, p=0.0073). The median survival time (MST) of the patients with high ERCC1 levels was significantly higher than that in patients with a low ERCC1 level (MST: not reached vs. 16M). Then, 30 more patients with the same backgrounds were added to the study, and ERCC1 mRNA levels were measured in all 50 patients. The patients with high ERCC1 mRNA levels had a significantly greater overall survival rate compared with those with low ERCC1 levels (MST: not reached vs. 12.5M, 5-year survival rate: 92% vs 51%; p=0.04). In multivariate analysis, no lymph node metastases or high ERCC1 expression were significantly associated with better overall survival. Conclusions: ERCC1 mRNA expression seemed to be a useful prognostic biomarker for extrahepatic cholangiocarcinoma with R0 resection.

Expression levels of ERCC1 and RRM1 mRNA and clinical outcome of advanced non-small cell lung cancer

We conducted a study to understand the genetic effect of ERCC1 and RRM1 on the chemotherapy response and clinical outcome of Non-Small Cell Lung Cancer (NSCLC). The relative cDNA quantification for ERCC1 and RRM1 was conducted using a fluorescence-based real-time detection method among 294 NSCLC patients. Compared with the internal reference gene β-action, the median levels of ERCC1 and RRM1 expression were 2.43×10(-2) and 0.11×10(-2), respectively. Our study showed response to platinum-containing regimen chemotherapy was high in those with high ERCC1 expression, and the OR (95% CI) were 1.73(1.06-2.81). An apparently high response to chemotherapy was decreased when patients were carrying both high expression of ERCC1 and RRM1, with OR (95% CI) of 2.57(1.21-4.90). Patients with high expression of ERCC1 were associated with a longer OS by multivariate Cox proportional hazards model. Moreover, those carrying both high levels of ERCC1 and RRM1 were seem to have a longer OS when compared with those with low expression (HR=0.31, 95% CI=0.13-0.62 for OS). This observation could be used in personalized chemotherapy, increase the response rate and prolonged survival time, and could encourage to explore the predictive value of other genes.

Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours

Background:Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs.Methods:The expression of ERCC1 and XPA and the presence of γH2AX were evaluated in cancer cell lines and in fresh ns-TGCTs. The ERCC1 protein was also determined in ns-TGCTs. The differences between CPS and non-CPS cell lines and patients were analysed by Student's t- or χ2-tests. The differences in OS were analysed using the log-rank test, and the hazard ratios (HRs) were calculated using the Cox model.Results:High ERCC1 expression was observed in the non-CPS cells, and both ERCC1 and γH2AX expressions were augmented after cisplatin treatment. Increased ERCC1 expression was also identified in non-CPS patients. Neither polymorphism was associated with either CPS or OS. The presence of ERCC1 was associated with non-CPS (P=0.05) and adjusted in the prognosis groups. The HR in ERCC1-negative and non-CPS patients was >14.43, and in ERCC1-positive and non-CPS patients the HR was >11.86 (P<0.001).Conclusions:High levels of ERCC1 were associated with non-CPS, suggesting that ERCC1 could be used as a potential indicator of the response to cisplatin and prognosis in ns-TGCTs.

Early recurrence in glioblastoma.

e13032 Background: Current standard treatment for glioblastoma (GBM) consists of surgical resection, radiotherapy of 6000 cGy to the tumor bed and concomitant then adjuvant temozolomide (TMZ). Median survival on this regimen is 14 months. Early recurrence on imaging studies can be conflicted with treatment effect. Six patients are presented who recurred locally within 7 months of diagnosis despite optimal treatment, in an effort to determine molecular characteristics of patients with early progression. Methods: Three patients underwent gross total tumor resection, 3 underwent subtotal resection. All received IMRT totaling 6000 cGy with concomitant TMZ, followed by adjuvant TMZ. Ages ranged from 23 to 71, median 56. Time to radiographic recurrence was 3 to 7 months, median 4.8 months. There are 5 males and one female. Tumor methylation status and other markers are presented. Results: Three of the 6 patients were re-operated and pathology consistent with recurrent GBM. The remaining 3 progressed neurologically and by MRI scan. The O-6-methylguanine-DNA methyltransferase (MGMT) promoter gene of one tumor was unmethylated. This tumor specimen also expressed topoisomerase II; EGFR and EGFR VIII were negative. One tumor specimen expressed the BRAF V600e mutation. Both of these latter specimens expressed high levels of ERCC1, a DNA repair enzyme which would render these tumors unresponsive to platinum compounds. Conclusions: MGMT promoter methylation status may not be the only predicter of early recurrence. Exploring other biomarkers in more patients with glioblastoma at the time of surgery may assist in predicting true early progression verses pseudoprogression, an imaging challenge, in patients who may respond to different agents.

Molecular predictors of treatment response in colon and gastric cancer.

619 Background: With the noted exception of KRAS mutational status, currently there exists limited data regarding the incorporation of tumor-derived biomarkers in the clinical management of gastrointestinal malignancies. High ERCC1 levels have been associated with inferior results in platinum-treated patients with non-small cell lung cancer, esophageal cancers, and head and neck cancer. Lenz et al. concluded ERCC-1 gene expression levels may allow the selection of patients who may benefit from FOLFOX chemotherapy in metastatic colon cancer. Low intra-tumoral ERCC1 mRNA expression predicted improved PFS and OS in patients with esophageal adenocarcinoma who were treated with tri-modality therapy in the SWOG 0356 correlative study. Methods: To determine the prevalence and patterns of expression of select tumor biomarkers including ERCC1, TS, HER-2, KRAS, BRAF, and EGFR gene expression was measured in metastatic gastric and colorectal cancers using formalin fixed paraffin embedded tumor samples from 120 metastatic colorectal and 20 metastatic gastric cancer were dissected using laser-captured micro-dissection and analyzed for ERCC-1, TS, EGFR, RRM1, and VEGFR2a mRNA expression using a quantitative RT-PCR methodology. Gene expression values (relative mRNA levels) were recorded as ratios between the target gene and internal reference gene (beta-actin). A retrospective review of the patient’s response to therapy was planned. Results: In colorectal patients, the incidence of KRAS mutations was 50%, specifically Gly12Ser 4%, Gly12Val 11%, Gly12Asp 20%, Gly12 Cys 7% Gly12Ala 2% and Gly13Asp 8%. BRAF expression analysis displayed 91% wild type with 9% V600E mutations. Median expression values for ERCC1, TS, EGFR, RRM1, and VEGFR2A expression levels using RT-PCR were 1.23, 2.28, 1.90, 1.05, and 1.61 respectively in the colorectal subset. In gastric cancer, ERCC1, TS, and Her-2 median expression levels using RT-PCR were 1.54, 3.56, and 0.08 respectively. Correlation with clinical outcome is pending and will be reported later.

Expression of DNA repair genes in ovarian cancer samples: Biological and clinical considerations

The purpose of this study was to investigate retrospectively the mRNA expression of genes involved in different DNA repair pathways implicated in processing platinum-induced damage in 171 chemotherapy-naïve ovarian tumours and correlate the expression of the different genes with clinical parameters. The expression of genes involved in DNA repair pathways ( PARP1, ERCC1, XPA, XPF, XPG, BRCA1, FANCA, FANCC, FANCD2, FANCF and PolEta), and in DNA damage transduction ( Chk1 and Claspin) was measured by RT-PCR in 13 stage I borderline and 77 stage I and 88 III ovarian carcinomas. ERCC1, XPA, XPF and XPG genes were significantly less expressed in stage III than in stage I carcinoma; BRCA1, FANCA, FANCC, FANCD2 gene expressions were low in borderline tumours, higher in stage I carcinomas and lower in stage III samples. High levels of ERCC1, XPA, FANCC, XPG and PolEta correlated with an increase in Overall Survival (OS) and Progression Free Survival (PFS), whilst high BRCA1 levels were associated with PFS on univariate analysis. With multivariate analyses no genes retained an association when adjusted by stage, grade and residual tumour. A tendency towards a better PFS was observed in patients with the highest level of ERCC1 and BRCA1 after platinum-based therapy than those given both platinum and taxol. The expression of DNA repair genes differed in borderline stage I, stage I and stage III ovarian carcinomas. The role of DNA repair genes in predicting the response in ovarian cancer patients seems far from being established.

Blood-based CHRNA3 single nucleotide polymorphisms (SNPs) and outcome in advanced non-small cell lung cancer (NSCLC) patients (p)

8033 Background: Nicotonic acetylcholine receptors (nAChRs) are associated with resistance to gemcitabine (gem), cisplatin (cis) and paclitaxel in NSCLC cell lines. Three SNPs of CHRNA3, CHRNA5 and LOC123688 increase lung cancer risk. These SNPs may have influenced outcome in p treated in our phase III trial (Cobo et al. J Clin Oncol 2007;25:2747–54). Methods: Stage IV NSCLC p were treated with customized chemotherapy based on ERCC1 mRNA expression. p in the control arm received docetaxel (doc)/cis; p in the genotypic arm with low ERCC1 levels (low genotypic group [LG]) received doc/cis; p in the genotypic arm with high ERCC1 levels (high genotypic group [HG]) received doc/gem. DNA was extracted from lymphocytes, and CHRNA3 (rs1051730), CHRNA5 (rs16969968) and LOC123688 (rs8034191) SNPs were genotyped with the Taqman allele discrimination assay. Results: A significant interaction was found for CHRNA3 and PS (P = 0.02). In p with PS 0, CT p had a better response than both CC (P = 0.01) and TT (P = 0.02) p, and LG p also had a better response (P = 0.01). When the CHRNA3 genotype was added in the multivariate analysis for progression-free survival (PFS), an improvement was observed in the LG in PS 0 p (P = 0.02). PS 0 p in the LG with the CT genotype attained an 84% response, 12.1-month PFS, and 19-month median survival (MS) ( Table ). Conclusions: CHRNA3 genotyping can improve customized chemotherapy based on tumor ERCC1 mRNA in stage IV NSCLC p with PS 0. [Table: see text] No significant financial relationships to disclose.

Gender Differences: Implications for Clinical Trials and Practice

Gender Differences: Implications for Clinical Trials and Practice

Factores de prognóstico no cancro do pulmão: Interesse clínico

Lung cancer, and in particular non small-cell lung cancer (NSCLC), remains the leading cause of cancer death throughout the world, with five years survival<15%. To determine individual prognostic factors that will influence response to chemotherapy and survival is not easy due to tumour heterogeneity.Many studies identify clinical, laboratorial and molecular factors, but probably due to differences in the methodology, there are many discrepancies, sometimes with opposite results.Nevertheless, relatively few prognostic factors such staging and Performance Status have been accepted as useful.In clinical practice, using a nomogram to predict survival with pre-treatment clinical factors could help clinicians and patients in clinical decision making.Genetic markers can be used to identify subgroup of patients that will have no response to chemotherapy. We know that patients with high ERCC1 levels do not respond to cisplatin-based chemotherapy, therefore we are able to avoid the lost of time, costs and toxicity.The knowing in accordance with the patient and tumour genetic profile could be useful not only for prognosis but for treatment.Molecular markers need to be validated in order to test its clinical utility.