If their ancestors help, weak cancer cells can form tough tumours Premium

Scientists uncover how cancer cells become drug-resistant by interacting with their ancestors, offering insights for future therapies.

Scientists have cracked the mystery of how some cancer cells that ought not to survive could actually take help from their ‘neighbours’ to succeed and form drug-resistant tumours instead.

Drug resistance is one of the world’s major crises of the 21st century. When a pathogen that causes an infection or disease becomes drug-resistant, drugs that could cure these conditions become less effective. Pathogens acquire this ability in the form of certain genetic mutations although some non-genetic factors are also in play.

When a cancer takes root in a person’s body, the cancer cells can also become drug-resistant in the same way. Simple logic dictates that when the person takes a drug to destroy these cells, the drug-resistant cells will proliferate while the non-resistant cells won’t. However, the genetic changes that conferred drug-resistance to the cells will also have undermined their overall ‘fitness’. When the person isn’t taking a drug to treat the cancer, the drug-resistant cells should thus have a harder time surviving than their non-resistant peers. They are said to suffer a ‘growth penalty’.

How the evolutionarily less-fit cells survive such conditions is a puzzle scientists have been trying to solve for years.

In past studies, scientists have tried to understand drug resistance by separating the corresponding cells from a larger population, making copies of them in the lab, and investigating them further. The researchers behind the new study realised this approach removes an important bit of context that could affect the cells’ prospects: the influence of other cells in their surroundings, especially the ancestors from which they ‘deviated’ by accumulating genetic changes.

Jeff Maltas, a postdoctoral research fellow at Cleveland Clinic and the lead author of the study, said scientists have appreciated the idea of tumours as a complex ecological system. He said his team’s idea came from multiple disciplines plus previous reports of high mutation rates within a tumour that had changes in pH and oxygen levels, among other conditions.

In a study published in 2022, for example, some members of the same team of researchers and others showed that even in the absence of a drug, drug-resistant mutant cells undergo large changes in growth rate. The authors attributed this to the environment in which the cells existed.