Why do bowel cancer tumours develop drug resistance?

Bowel tumours are made up of cancer cells which have evolved from the patient’s original, normal cells.

As these cells compete for survival, they will accumulate all sorts of mistakes (mutations) in the instructions in their genetic code, as well as much larger changes when whole chromosomes are lost or gained. Ongoing changes at this larger scale are referred to as chromosomal instability (or CIN).

The problem is also highly prevalent – with over 50% of metastatic cancers displaying resistance to some of the most common chemotherapy drugs.

Why target Chromosomal Instability (CIN) to improve treatment?

CIN has been linked to more aggressive tumour progression and worse patient outcomes. The more they shuffle their genome around, the more chance these unstable cancer cells have to adapt to their challenging environment and resist attempts to destroy them with chemotherapy.

Researchers funded by Bowel Research UK have found that unstable cancer cells grown in the lab can be treated with drugs to reduce their chromosome instability, slowing these changes down. They now want to measure how stable the treated cells are, based on their DNA sequence, using advanced single-cell sequencing technology, and see if this reduces their ability to develop resistance to chemotherapeutic drugs.

What could success mean?

Success in this work could ultimately make chemotherapy more efficient in killing cancer cells before a patient’s tumour develops drug resistance. This work will establish whether targeting chromosomal instability is a strategy worth pursuing to achieve this.

The research team

The research will be led by Dr Nadeem Shaikh at the National Bowel Research Centre, Blizard Institute in London.