Cancer cellsResearchers at King’s have achieved a breakthrough in understanding a biological process which causes many common cancers, including lung and breast cancer. The achievement opens up new possibilities for the development of improved cancer drugs. The findings are published in the journal Molecular and Cellular Biology.
Working with the Science and Technology Facilities Council (STFC) Central Laser Facility (CLF) and Computational Science and Engineering Department (CSED), the team solved a puzzle that has confounded scientists for more than 30 years.
The researchers have discovered a previously unknown molecular shape which is partly responsible for transmitting the signals that instruct cells within the body when to grow and divide. It is the uncontrolled growth of cells that causes cancer to spread through the body. Until now, not enough was known about how these molecules, known as epidermal growth factor receptors (EGFRs), transmit messages in the development of cancer. This means drugs designed to stop them transmitting these cancer-inducing signals have also been limited in their effectiveness.
Professor Peter Parker, Head of the Division of Cancer Studies, is the Principal Investigator at King’s College London on the research. Dr George Santis, head of the department of Asthma Allergy and Respiratory Science at King’s, will help take this work forward. He said: ‘Translating knowledge derived from scientific research into successful clinical therapies is exemplified by EGFR and its dysregulation in cancer. The use of new biologicals that inhibit EGFR has proved transformational in managing solid tumours, particularly lung cancer where conventional anti-cancer treatment reached a plateau. There is however still much we don't understand regarding EGFR and its role in malignancy; this breakthrough provides the foundation for novel ways to assess EGFR in cells and tissues that may lead to new insights on how to target EGFR to treat human cancers’.
Project leader Dr Marisa Martin-Fernandez, a CLF scientist based at the Research Complex at Harwell (RCaH), says: “A number of drugs aim to limit EGFRs’ role in spreading cancer but because human EGFRs haven’t been well understood, the drugs are designed simply to block every signal they transmit. But the human body is good at compensating for losses of function so it finds ways of bypassing blocked receptors to allow cancerous cells to grow again. Unfortunately the current drugs therefore all too often only provide temporary remission.
“Our breakthrough will provide a better platform of knowledge on structure variation of EGFRs in vivo. Potentially this enables the pharmaceutical industry to develop drugs that target EGFRs’ cancer-related functions more specifically but also allow the receptors to go on performing other tasks. This makes it less likely that the body will try to compensate for total loss of function.”
The team has also shown that this shape shares key features with the better understood EGFR molecules in fruit flies, providing clues on how EGFRs have changed during evolution.
Details of the breakthrough are presented in the paper ‘Human EGFR aligned on the plasma membrane adopts key features of Drosophila* EGFR asymmetry’, and are featured on the front cover of the current edition of the journal Molecular and Cellular Biology published today.
The work was carried out with funding from Biotechnology and Biological Sciences Research Council (BBSRC).
Notes to editors
The BBSRC award is a £5.2M ‘LoLa’ (longer and larger) grant secured jointly by STFC and King’s College London in 2009. The research summarised in this release represents just one aspect of the work being supported by this funding.
OCTOPUS (Optics Clustered to Output Unique Solutions) is a new concept in laser imaging, in which multiple light sources are linked to multiple imaging stations allowing a combination of techniques to be brought to bear on the samples under investigation. More information can be found here. http://www.clf.stfc.ac.uk/Facilities/Lasers+for+Science+Facility/Functional+Biosystems+Imaging+Group/OCTOPUS/14219.aspx
*Drosophila is the Latin name for the fruit fly. Fruit flies are often used in biology to understand more about the inner workings of cells.
King's College London
King's College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times 'University of the Year 2010/11' and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.
King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org
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