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Cancer, DNA

From petri dish to personalised medicine

Bowel cancer is one of the most common forms of cancer. In 2011, over 40,000 people in the UK were diagnosed with the disease1: equivalent to one person every 15 minutes. In order to try and understand how and why this form of cancer develops, scientists need to be able to grow cells derived from tumours in the lab – something which has proven to be extremely challenging. However, researchers in Walter Bodmer’s group at the WIMM have recently developed a method to not only propagate these rare tumour samples in the lab, but also to coax them to develop into structures similar to those found in the bodyBryony Graham explains more.

The normal function of each and every cell in your body is controlled by its very own copy of your DNA, which is otherwise known as your genetic code. This code is unique to you (unless you have an identical twin) and is critical to your development and survival. It’s therefore hardly surprising that if for some reason your DNA is damaged, this often has a devastating impact on your health.

Cancer develops when the DNA in your somatic cells (that is, those cells that are not passed on to your children) is damaged in several places, and the accumulation of these changes gradually alters the behavior of the cell until it begins to grow uncontrollably, eventually forming a tumour.

PetriDishRecent technological advances in machines which are able to read the genetic code very quickly and cost-effectively have allowed scientists to start to find out when, where and how often these changes occur in DNA. It is now becoming apparent that two people with the same form of cancer very rarely have the same set of changes to their DNA – but there are some culprits which appear more frequently than others. The challenge that scientists now face is to work out why these specifc changes are found more often than others, and what exactly they are doing to the cell.

To tackle this problem, scientists need to be able to take samples from tumours where different bits of the DNA have been damaged, and see how the cells within the tumour function differently to normal cells. But can you take a cell out of a tumour sample and expect it to behave in exactly the same way in a petri dish as it does inside your body?

The answer is yes – but with great difficulty. Scientists have been trying to find a way to do this for several years, but with limited success. Recently, however, researchers in Walter Bodmer’s group in the Department of Oncology at the WIMM have developed a method of taking cells directly from patient tumours, growing them in highly specialized plastic dishes, and coaxing them into forming structures which would normally be found inside the colon in the body.

This video (originally published as part of the research paper) shows one such structure, called a colon cancer colony, which has been grown in the Bodmer lab from cells taken from a patient. The normal colon consists of several types of specialised, or differentiated, cells that are constantly regenerated from a long-lived and non-specialised pool of stem cells. Cancer stem cells are of great interest as they are the cells that drive the cancer growth. Here, the cancer colony can be seen to be ‘spitting out’ abnormal cells that eventually die. The Bodmer group have shown that these abnormal ‘bubble’ cells are highly differentiated and are probably derived from the cancer stem cell population, a process similar to that which occurs in patient cancers.

This novel system holds huge potential for allowing scientists to finally understand just what exactly all those changes to the DNA are actually doing to cells, and how this leads to the development of tumours. This level of comprehension holds huge promise therapeutically: if different tumours have a different set of changes to the DNA code, they might also respond differently to anti-cancer drugs. This level of specificity has already been shown in breast cancer, and has helped to develop personalized therapeutic strategies for individual patients based on their DNA. Whilst this level of personalized medicine is a long way off for most diseases, findings like those from Walter Bodmer’s group start to bring such possibilities ever closer.

  1. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/bowel/
  2. http://www.bowelcanceruk.org.uk/information-resources/bowel-cancer-facts-figures/
  3. http://onlinelibrary.wiley.com/doi/10.1002/path.4371/abstract;jsessionid=059E7F62839661ED809C8A9007202C81.f01t01

Post edited by Walter Bodmer, Neil Ashley and Jennifer Wilding.

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