Pre-treatment molecular stratification and the histogenic origins of rectal cancer
Rectal cancer affects 11,000 people per year in the UK. Currently we cannot predict which tumours will respond best to which therapy. There are two main types of polyps that can develop into rectal cancer; we believe one type (TSA) leads to more aggressive cancers that are not sensitive to radiation but may be sensitive to new highly-specific chemotherapeutic agents. However, by the time the cancer has developed, standards tests cannot determine which polyp type it came from. If we had this information each patient could receive the most appropriate treatment, and only patients who were likely to benefit from radiation would be exposed to it.
By looking at genetic material from the two polyp types, we are developing a panel of molecular tests to distinguish the types. We will then apply this test to a large group of rectal cancers that have been surgically removed and determine what proportion originated from the more aggressive type. We will compare cancers originating from the two polyp types with clinical outcomes and sensitivity to radiation to determine whether TSA-origin rectal cancers are more aggressive and less responsive to radiotherapy compared with other rectal cancers.
We expect this will provide a valuable pre-therapeutic biomarker to determine early whether a cancer is the more aggressive type, allowing treatment to be individualised for each patient.