Publications
BCI Honorary Clinical Lecturer contributes to landmark paper in tumour biology
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Dr Marco Gerlinger, an honorary clinical lecturer at Barts Cancer Institute and a clinician scientist at Cancer Research UK is first author of a groundbreaking new paper* exploring the genetic differences within individual tumours. Using samples taken from different parts of four separate kidney tumours, and also from sites where the cancer had spread to other organs, Dr Gerlinger and his colleagues carried out the first ever genome-wide analysis of the genetic variation between different regions of the same tumour. They found that between 63-69% of gene faults were not shared across other biopsies from the same tumour. The findings could help explain why attempts at using single biopsies to identify biomarkers to which personalised cancer treatments can be targeted have not been more successful - but also opens the door to treatment improvements. Dr Gerlinger explains the feat of this research; "We tried to answer a simple but important question: Are the same genetic defects that determine tumour aggressiveness and potential treatment failure present throughout individual tumours or is there regional variation within tumours? The diversity we found in the genetic blueprints within tumours was simply astonishing. This is a major step forward to better understand cancer biology and may explain why tumours rapidly develop drug resistance and why it is so difficult to predict tumour aggressiveness from the small tumour biopsies routinely used in the clinic. We are now working towards robust methods to detect intra-tumour heterogeneity that can be used in the clinical setting and on novel drug treatment strategies which could improve patient outcomes by focusing on common genetic defects present in all cells of a tumour." *Gerlinger M. et al, Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing. New England Journal of Medicine 2012. |
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Cutting off the Oxygen Supply to Serious Diseases
Work by Dr Tyson Sharp and his group leads to discovery of new protein
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A new family of proteins called 'LIM domain containing proteins,' which regulate the human body’s ‘hypoxic response’ to low levels of oxygen has been discovered by scientists at Barts Cancer Institute at Queen Mary, University of London and The University of Nottingham. The researchers have uncovered a previously unknown level of hypoxic regulation at a molecular level in human cells which could provide a novel pathway for the development of new drug therapeutics to fight disease. Cancer cells have a faulty hypoxic response which means that as the cells multiply they highjack the response to create their own rogue blood supply. In this way the cells can form large tumours. The new blood supply also helps the cancer cells spread to other parts of the body, called ‘metastasis’, which is how, ultimately, cancer kills patients. The discovery has been published in the latest issue of the journal Nature Cell Biology. It marks a significant step towards understanding the complex processes involved in the hypoxic response which, when it malfunctions, can cause and affect the progress of many types of serious disease, including cancer.
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BCI Research Discovers Vitamin A Key to Fighting Cancer - the next step in the 'Seed and Soil' theory
Vitamin A could hold the key to beating pancreatic cancer which has the lowest survival rate of all cancers.
An international research team, led by researchers at the Barts Cancer Institute (BCI), has found that by raising levels of Vitamin A in non-cancerous cells surrounding malignant ones, they were able to change the cells’ structure so as to inhibit rather than facilitate cancer growth.
"These exciting research findings are proof of principle that novel promising routes can be used to devise new treatments for deadly diseases such as pancreatic cancer."
Mr Hemant Kocher
Mr Hemant Kocher, a consultant pancreatic and liver cancer surgeon, led the team during a four year joint project with the University of Cambridge and the Hubrecht Institute in Holland. These findings have now been published in the prestigious journal: Gastroenterology.
Pancreatic cancer is a deadly disease which kills almost 7,500 patients in the UK and quarter of a million people world-wide.
Once diagnosed with pancreatic cancer most patients do not survive more than 1 year and a few (less than 20%) who have surgery and chemotherapy may survive more than 2 years.
It is rare for pancreatic cancer patients to survive more than 5 years.Thus, new methods for treating this cancer are urgently required.
This research adds more evidence for the concept of the ‘seed and soil’ theory for targeting cancer, initially proposed in 1889, by Stephen Paget, a surgeon at St Bartholomew’s Hospital.
Dr Paget studied why breast cancer prefers to spread into certain organs, like the liver and the bone, rather than other areas of the body. He believed those organs provided a more fertile environment in which the cancer could seed itself.
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This ‘seed and soil’ theory has been taken a major step forward in the recently published work from Hemant Kocher's group. Now they are proposing that paying attention to the "soil" in the immediate vicinity of the cancerous cells (i.e. the surrounding non-cancerous tissues) may be as important as targeting the cancer itself.
Pancreatic cancer patients are deficient in many vitamins due to a blockage in the secretion of digestive juices from the pancreas and liver. One such vitamin is Vitamin A, commonly found in vegetables such as carrots.
Mr Kocher and his team demonstrated that restoring normal amounts of Vitamin A in vitamin-storing cells of the pancreas (called stellate cells) turns these stellate cells from cancer-facilitating cells to cancer-inhibiting cells.
Vitamin A treatment did not effect the cancer cells directly. Thus changing the surrounding tissue of pancreatic cancer changed the manner in which the cancer behaved.
Mr Kocher says these exciting research findings are proof of principle that novel promising routes can be used to devise new treatments for deadly diseases such as pancreatic cancer. This concept will need to be proved in clinical trials.
Journal Article:
Retinoic Acid-Induced Pancreatic Stellate Cell Quiescence Reduces Paracrine Wnt-β-Catenin Signaling to Slow Tumor Progression.
Froeling FE, Feig C, Chelala C, Dobson R, Mein CE, Tuveson DA, Clevers H, Hart IR, Kocher HM.
