Understanding genetics of oesophageal treatment hoped to improve treatment

23 May 2015

Francis Crick Institute scientists have identified specific patterns of change that occur early in the development of oesophageal cancer and may be related to exposure to stomach acid, as well as changes that happen following chemotherapy. The work has implications for treating patients with the disease.

Dr Charles Swanton of the Crick said: "The aim of this study was to improve understanding of how cancers of the oesophagus (the food pipe that runs between the throat and stomach) may change over time and adapt following chemotherapy.

"If we can identify which genomic faults occur early during tumour development and are present in all tumour cells, and which occur later, present only in a subset of tumour cells, it may be possible to develop therapeutic approaches to improve survival."

The researchers took biopsies from different parts of tumours from eight patients with oesophageal cancer and used the latest technology to analyse these and obtain a comprehensive genomic profile.

Dr Swanton said: "Different parts of a tumour can change independently; so one region of the tumour may contain different genetic changes than another region of the same tumour. This allowed us to determine the early changes in tumour evolution that potentially contributed to the original formation of the cancer. It also enabled us to identify specific mutational patterns or signatures that may be related to the development of the tumour over time."

The researchers also identified cancer-related genes that were likely to be present at multiple copies in all the cells within the tumour. These were seen both before and after treatment with chemotherapy, potentially providing new drug targets.

The group's results showed that more genetically diverse tumours tended to respond poorly to chemotherapy given before surgery. They also detected patterns of mutation within the cancer cells that could actually have been driven by chemotherapy using drugs based on platinum, highlighting the need to identify patients who will not benefit from this treatment.

Dr Swanton said: "Our work provides insight into how oesophageal tumours evolve over time.

"We identified potential targets for new treatments, by identifying regions of DNA that include important cancer related genes. These could provide a stable target for therapy."

The paper, Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy, is published in Cancer Discovery.

  • Genetic insights into the development of oesophageal cancer and its response to treatment are hoped to lead to improved treatment.
  • The research was carried out by scientists from the Francis Crick Institute (currently based at Lincoln's Inn Fields), University College London and Imperial College London.