Why do damaged cells sometimes continue to multiply instead of eliminating themselves?

Every cell has built-in self-destruct mechanisms, but damaged cells can bypass them in several ways. One way is through rapid DNA repair: cancer cells with high activity of the protein KIN17 (a DNA repair protein) patch up damaged sections of genetic material so quickly that the alarm triggering self-destruction never goes off. When KIN17 was switched off in experiments, DNA damage accumulated and cell division stopped.

A second way is blocking the self-destruction signal itself. Normally, radiation or chemotherapy prompts damaged cells to undergo apoptosis, an orderly self-destruction process. Cancer cells can actively block the signals that initiate this process. That blockade is also one of the main reasons why tumours gradually respond less well to treatment over time.

In addition, cancer cells can hijack another clean-up system, autophagy (in which the cell digests its own damaged components), and turn it to their advantage. In the early stages of cancer, this process still protects the body. Later in the disease, tumour cells use that same system to survive under stress instead of eliminating themselves.

Things also go wrong outside the cell. After a cell dies via apoptosis, immune cells must clear the remains through a process called efferocytosis. When that clean-up falters, cell debris accumulates and inflammation develops. Cancer cells can actively evade this clean-up process, leaving the debris in place. Finally, aggressive tumour cells make themselves difficult for the immune system to recognise, causing the surveillance that normally detects abnormal cells to let them pass. Cancer cells can also flexibly switch between energy sources, which helps them survive chemotherapy.

All these mechanisms reinforce one another. There is no single escape route: a damaged cancer cell often uses several at the same time.