Chemotherapy for Colorectal Cancer

Goyle, Sandeep; Maraveyas, Anthony

doi:10.1159/000091441

Cited by 52 publications

(39 citation statements)

References 114 publications

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“…The development and approval of novel therapies, including the monoclonal antibodies bevacizumab (anti-vascular endothelial growth factor; Avastin) and cetuximab (anti-EGFR), have increased median survival of patients with metastatic colon cancer to f24 months (34,35).…”

Section: Discussionmentioning

confidence: 99%

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

et al. 2008

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Cetuximab is a monoclonal antibody that targets the human epidermal growth factor receptor (EGFR). Although approved for use in EGFR-overexpressing advanced colorectal cancer, recent studies have shown a lack of association between EGFR overexpression and cetuximab response, requiring the identification of novel biomarkers predictive of response to this agent. To do so, 22 colon cancer cell lines were screened for cetuximab response in vitro and sensitive and resistant lines were identified. In sensitive cell lines, cetuximab induced a G 0 -G 1 arrest without inducing apoptosis. Notably, cetuximabsensitive but not cetuximab-resistant cell lines were preferentially responsive to EGF-stimulated growth. Whereas neither EGFR protein/mRNA expression nor gene copy number correlated with cetuximab response, examination of the mutation status of signaling components downstream of EGFR showed that cell lines with activating PIK3CA mutations or loss of PTEN expression (PTEN null) were more resistant to cetuximab than PIK3CA wild type (WT)/PTENexpressing cell lines (14 F 5.0% versus 38.5 F 6.4% growth inhibition, mean F SE; P = 0.008). Consistently, PIK3CA mutant isogenic HCT116 cells showed increased resistance to cetuximab compared with PIK3CA WT controls. Furthermore, cell lines that were PIK3CA mutant/PTEN null and Ras/BRAF mutant were highly resistant to cetuximab compared with those without dual mutations/PTEN loss (10.8 F 4.3% versus 38.8 F 5.9% growth inhibition, respectively; P = 0.002), indicating that constitutive and simultaneous activation of the Ras and PIK3CA pathways confers maximal resistance to this agent. A priori screening of colon tumors for PTEN expression status and PIK3CA and Ras/BRAF mutation status could help stratify patients likely to benefit from this therapy.

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Section: Discussionmentioning

confidence: 99%

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

et al. 2008

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“…Protracted infusional regimes were developed to maximise 5FU dose intensity. They have been found to be as effective as the bolus regimens and less toxic, with less impact on quality of life (Andre et al, 2003;Saini et al, 2003;Goyle and Maraveyas, 2005 (Goyle and Maraveyas, 2005). The other major factor likely to result in failure to complete chemotherapy is toxicity.…”

Section: Discussionmentioning

confidence: 99%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR ¼ 2.24; 95% confidence interval (CI) (1.66 -3.03), Po0.001) but also to those treated by surgery alone (HR ¼ 1.37; 95% CI (1.09 -1.72), P ¼ 0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made.

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“…As important group of antineoplastic drugs, 5-fluoropyrimidines and pemetrexed could target on TS, and are widely used in the treatment of gastrointestinal tumors, breast tumors, and epithelial tumors of the upper aero digestive tract (Grem, 1988;Goyle et al, 2006). Previous studies performed on several cancers have demonstrated that the TS expression level predicted the response to 5-FU or pemetrexed chemotherapy (Foekens et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Multiplex Real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for Prediction of Response of Non-small Cell Lung Cancer to Chemoradiotherapy

Liu²,

Xue³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III β-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatinbased first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.

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Chemotherapy for Colorectal Cancer

Cited by 52 publications

References 114 publications

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Multiplex Real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for Prediction of Response of Non-small Cell Lung Cancer to Chemoradiotherapy

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