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MRC Toxicology Unit

 

Thoracic tumour biology

Lead Pathologist: Dr John Le Quesne MBBS FRCPath

 

Summary of Research Interests

Lung cancer is responsible for more deaths than all the other common cancers, and treatment options remain limited for many patients. While experiments using human and animal cells can tell us a great deal, there is no substitute for the study of primary human tumour tissues.

We are developing a range of techniques to obtain the most information possible from resected human tumour materials. We are assembling very large retrospective series of tumour material, and accompanying clinical data, digital microscopic images, tissue microarrays and nucleic acids:

Retrospective Tissue Pipeline

 

Collections of primary human non-small cell lung carcinomas and mesotheliomas are largely complete; for example, over 1000 primary adenocarcinomas have been fully incorporated into our collections. This is an extremely powerful resource for both discovery science and hypothesis testing.

 

Current active projects include:

  1. Molecular and morphological characterisation of the switch from in situ to invasive behaviour in early primary lung adenocarcinomas
  2. The discovery of clinically useful biomarkers to guide the administration of chemotherapy and radiotherapy
  3. The effects of sex hormone signalling in adenocarcinoma
  4. Improved prognostic biomarkers in NSCLC
  5. The clinical and phenotypic consequences of altered translational control

 

In addition to these tissue-based projects, we have long-standing interests in the control of mRNA translation, and how this is altered in malignant cells. We are addressing these issues in cell culture models as well as in tumour tissues. Key research questions in this area include:

  1. How can we detect and quantify translational dysregulation in tumour tissue?
  2. How is translational dysregulated related to patient outcome, to tumour behaviour, and to cellular phenotypes within tumours?
  3. How do alterations in the mRNA translation apparatus influence message-specific translation of mRNAs?