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Tumour heterogeneity and tumour microenvironment in lung cancers

The RuBICON project (Rule Book and Immune atlas for COmbinatioN therapy) utilises new microscopic imaging technology to enhance the characterisation of tumours and the tumour microenvironment.

Applications are now closed for the 2019 postgraduate training programme.

  • Primary Supervisor: Dr Mariam Jamal-Hanjani, UCL Cancer Institute and Prof Charles Swanton, the Crick
  • Secondary Supervisors:  Prof Karibaan Hodivala-Dilke, Barts Cancer Institute, QMUL and Dr David Moore, UCL Cancer Institute

Funding note: Non-EU candidates are not eligible to apply 

Background

Lung cancer is globally the biggest cause of cancer-related death, resulting in almost 1.6 million deaths per year. It is the third most common cancer in the United Kingdom. Non- small cell cancer (NSCLC) which makes up 85% of cases, and small cell cancer (SCLC), which makes up 15% of cases. In recent years, cases of long-term survival in advanced disease have been reported, due to targeted therapies and immune therapies. However, within the groups of patients who respond well to these therapies, a large number will eventually develop resistance to treatment and experience a disease recurrence. Hence, there is a critical need to identify both new biomarkers predictive of disease behaviour, and potential actionable therapeutic targets.

Project

The RuBICON project (Rule Book and Immune atlas for COmbinatioN therapy) utilises new microscopic imaging technology to add further dimensions to the characterisation of tumours and the tumour microenvironment. The study uses tumour tissue from patients enrolled in the TRACERx study (a flagship CRUK study, which is the largest longitudinal cohort study of lung cancer evolution to date) and the PEACE study (also a flagship CRUK study, and the only study in the world to follow tumour evolution to after patient death). Both studies are UK-wide and facilitate collaborations between clinicians and scientists across the country. The RuBICON study uses imaging mass cytometry (IMC), which allows visualization of numerous different cell types with different protein expression patterns, to see how they behave in relation to each other.

This is a collaborative project, which applies novel microscopic imaging methods to samples from advanced NSCLC, correlating it with genomic and transcriptomic data from TRACERx and PEACE. Working with world-class experts in tumour micro-environment research, we will correlate data with tumour micro-environment behaviour, to understand better the process of cancer progression and treatment response. This will have a particular focus on tumour-infiltrating lymphocytes, tumour angiogenesis and cancer-associated fibroblasts. Overall, this project aims to work towards identifying both potential biomarkers of tumour behaviour, and actionable therapeutic targets. Therefore, this project will enable the candidate to explore the behaviour of NSCLC with a highly multi-dimensional perspective and translational aims.

The successful applicant will be able to demonstrate an interest in the tumour microenvironment, novel microscopic imaging technology and tumour evolution. They will work within a dynamic multidisciplinary team, comprising basic and clinical cancer immunologists, cancer biologists, pathologists, oncologists and bioinformaticians across multiple sites. Hence, they will be someone who works well in a large, multi-disciplinary setting. Given the role of complex image analysis in this project, it is ideally suited for a clinical trainee in histopathology. However, a training number in oncology will also be an advantage.

Potential Research placements

  1. Statistical analysis, bioinformatics, and novel microscopic imaging techniques. Research on the tumour microenvironment, supervised by Prof Hodivala-Dilke, Barts Cancer Institute, QMUL.
  2. Training with Bioinformaticians and cancer immunologists. Dr Nicholas McGranahan, UCL, Dr Erik Sahai, the Crick and Professor Sergio Quezada, UCL. 
  3. Participation in UCL Cancer Institute’s Training Programme for Researchers which incl.  bioinformatics, proteomics, microscopy, statistics, and biobanking seminars and courses.

References

  1. Angelova M. et al. Evolution of Metastases in Space and Time under Immune Selection. Cell, 2018; 175, 751-765.e16-765.e16.
  2. Caswell DR, Swanton C. The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome. BMC Medicine, 2017; 15, 133.
  3. Hiley CT. et al. Deciphering antitumour response and resistance with intratumour heterogeneity (DARWIN II). Journal of Clinical Oncology, 2017; 35, TPS9099.
  4. Jamal-Hanjani M. et al. Tracking the Evolution of Non–Small-Cell Lung Cancer. The New England Journal of Medicine, 2017; 376, 2109-2121.
  5. Wong PP. et al. Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread. Cancer Cell, 2015; 27, 123-37.