Dataset Information

TRANSlational Cancer Oesophagus Gefitinib study (TRANS-COG)

ABSTRACT: Background and study aims Oesophagogastric cancer refers to cancer of the stomach or oesophagus (also known as the gullet or food pipe). The COG study aimed to compare the effectiveness of an experimental drug called Gefitinib with placebo (dummy) tablets in patients with advanced oesophagogastric cancer. Gefitinib works by blocking an important receptor on the surface of cancer cells called the Epidermal Growth Factor Receptor or EGFR. It has been shown in lung cancer that patients whose tumours have mutations in the gene for EGFR respond very well to Gefitinib treatment. Gefitinib has been shown to be of benefit in some other types of cancer and tumour shrinkage has been demonstrated in some small studies of patients with oesophageal cancer treated with gefitinib. In the TRANSCOG study we are planning to analyse tumour samples for EGFR gene and other similar gene mutations to find out whether their presence in oesophageal cancers can predict which patients will respond and benefit from Gefitinib treatment and which will not. If this is possible we will be able to develop tests to allow us to target treatment to those patients most likely to respond and benefit from this treatment, and in those patients who are unlikely to respond we can avoid using a treatment that will not work and potentially try other treatments which may have a better chance of success. Who can participate? Oesophagogastric cancer patients aged over 18 who participated in the COG study. What does the study involve? Partcipants will be asked to sign a consent form to allow us to analyse a sample of their tumour tissue that has already been obtained during previous endoscopy and biopsy of your cancer or at the time of previous surgery. Participants will not need to undergo any extra tests, treatments or procedures to participate in the TRANSCOG study.

DISEASE(S): Upper Gastro-intestinal Cancer

PROVIDER: 2415632 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Similar Datasets

Project description:Basal-like and triple negative breast cancer (TNBC) share common molecular features, poor prognosis and a propensity for metastasis to the brain. Amplification of EGFR occurs in ~50% of basal-like breast cancer and mutations in the epidermal growth factor receptor (EGFR) have been reported in up to ~ 10% of Asian TNBC patients. In non-small cell lung cancer several different mutations in the EGFR tyrosine kinase domain confer sensitivity to receptor tyrosine kinase inhibitors, but the tumourigenic potential of EGFR mutations in breast cells and their potential for targeted therapy is unknown. Constructs containing wild type, G719S or E746-A750 deletion mutant forms of EGFR were transfected into the ‘near normal’ MCF10A breast cells and their tumorigenic derivative, MCF10CA1a. These transfected lines were used to investigate the effects of EGFR over-expression and mutation on proliferation, migration, invasion, response to gefitinib, and tumour formation in vivo. We also carried out copy number analysis and whole exome sequencing of the MCF10A and MCF10CA1a cell lines. Both activating mutations of EGFR increased the proliferative ability of MCF10A and MCF10CA1a cell lines, and increased the anchorage-independent growth and sensitivity to gefitinib in MCF10A cells. In addition, the EGFR-E746-A750 deletion increased the migratory and invasive abilities of the MCF10CA1a cell line in vitro, and greatly increased the formation and growth of MCF10CA1a tumours in vivo. Compared to MCF10A cells, MCF10CA1a cells had large regions of gain on chromosome 9 and the long arm of chromosome 3, deletion in the short arm of chromosome 7, and mutations in many genes implicated in cancer. The EGFR E746-A750 deletion mutation, and to a lesser extent G719S, greatly enhance the oncogenic properties of MCF10A cell line, and increase sensitivity to gefitinib. Although the addition of EGFR E746-A750 renders the MCF10CA1a cells more tumourigenic in vivo it is not accompanied by increased sensitivity to gefitinib, perhaps because of additional mutations, including the PIK3CA H1047R mutation, that the MCF10CA1a cell line has acquired. Screening TNBC/basal-like breast cancer for EGFR mutations may prove useful for directing therapy but, as in non-small cell lung cancer cancer, accompanying mutations in PIK3CA may confer gefitinib resistance.

Dataset Information

TRANSlational Cancer Oesophagus Gefitinib study (TRANS-COG)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets