Autophagy, a word that literally means “self-eating”, is one of the principal recycling systems within our cells. When a protein, cellular structure or organelle becomes worn out or damaged, the cell encloses it within a membrane and delivers it to compartments known as lysosomes. There, enzymes act as chemical tools, breaking the material down into smaller components that the cell can reuse to generate energy or build new structures. It is a continuous process that takes place, to varying degrees, in virtually all our cells.
Its discovery is also a story of patience. The Japanese scientist Yoshinori Ohsumi studied yeast—the microscopic fungi used to make bread and beer—under conditions of nutrient deprivation. He observed how cells accumulated structures involved in breaking down and recycling their own components, and he identified the genes essential to this process. His work helped to reveal much of the molecular machinery of autophagy and earned him the Nobel Prize in Physiology or Medicine in 2016.
Beyond its importance in maintaining cellular health and its relationship with ageing, autophagy has attracted considerable interest in cancer research. Cancer develops when cells acquire alterations that disrupt the mechanisms controlling their growth and survival. Understanding how autophagy contributes to this process is an important area of research in cancer biology.
An Internal Surveillance System: Autophagy helps to maintain cellular quality through several mechanisms.
One of these involves the removal of damaged mitochondria, the structures that produce much of the energy a cell requires. When a mitochondrion malfunctions, it may generate increased amounts of reactive oxygen species. These molecules form part of normal cellular processes, but when they accumulate excessively, they can damage various cellular components, including DNA. The selective removal of damaged mitochondria is known as mitophagy and helps to preserve the quality of these organelles.
Another mechanism enables cells to eliminate damaged proteins, or proteins that have accumulated abnormally. Autophagy forms part of a complex quality-control network that also includes other systems responsible for breaking down cellular components. When these mechanisms become impaired, cellular stress increases and inflammatory signals may be amplified. If this persists over time, it can contribute to an environment that favours certain processes involved in cancer.
Autophagy also plays a role in the functioning of the immune system. It contributes to the activity of different immune cells and to the processes involved in recognising and eliminating altered cells. Its relationship with the immune response against cancer, however, is complex and depends on both the cell type and the surrounding context.
The evidence that impaired autophagy can favour the development of some tumours is particularly strong in experimental models. Mice in which the activity of certain genes essential for autophagy is reduced develop some tumours more readily. One such gene is BECN1, which contains the instructions for producing Beclin 1, an important component of the autophagic machinery. In some human cancers, the loss of one copy of the chromosomal region containing this gene has also been observed.
These findings support a protective role for autophagy against certain tumour-related processes, although results obtained in animals cannot automatically be extrapolated to humans.
When the System Fails: When autophagy is insufficient, damaged cellular components can accumulate and increase cellular stress. Persistent disruption of these quality-control mechanisms may promote cellular instability and contribute to the development of some forms of cancer.
Ageing is also accompanied by changes in several components of the autophagic machinery. Experimental studies point to reduced efficiency in some of the mechanisms responsible for removing damaged cellular components, although this process varies between tissues and remains incompletely understood in humans.
Researchers are therefore investigating whether age-related changes in autophagy contribute to the increasing incidence of cancer in later life. It is a scientifically plausible hypothesis, but it does not by itself explain why cancer becomes more common with age.
The Other Side of the Coin: This is where the story becomes more complicated, and it is important to tell it honestly.
Once a tumour has become established, autophagy can serve as a survival mechanism for its cells. Tumours often grow rapidly, and some areas receive little oxygen and have limited access to nutrients. Under these conditions, certain tumour cells rely on autophagy to recycle their own components and obtain the resources they need to survive.
This mechanism can also contribute to resistance to certain treatments. Researchers are therefore investigating whether blocking autophagy can make some tumours more vulnerable to chemotherapy, radiotherapy or targeted therapies.
Some tumours, including certain forms of pancreatic cancer, appear to be particularly dependent on autophagy. For this reason, drugs capable of interfering with the process have been studied, including hydroxychloroquine, a medicine that has been used for decades to treat several diseases. The clinical trials conducted so far have produced limited results and have not demonstrated a consistent survival benefit.
The conclusion is that autophagy is neither inherently beneficial nor harmful. Under some circumstances, it protects healthy cells and helps to maintain their internal balance. Under others, established tumour cells can exploit it to survive. Its effects depend on the cell type, the alterations it carries, the stage of the disease and the environment surrounding it.
What Can We Do in Everyday Life?: Here, it is important to distinguish carefully between what we know and what remains under investigation.
Physical exercise, nutrient availability and fasting influence the metabolic pathways that regulate autophagy. However, the response depends on the type of exercise, its intensity, its duration and the tissue being studied. What happens in muscle after exercise does not necessarily occur in the same way in the liver, brain or adipose tissue.
Fasting also affects pathways related to autophagy, but we still do not know precisely how strongly this process occurs in different human tissues, or how long a period of dietary restriction must last to produce a particular effect.
It is therefore an exaggeration to claim that a specific number of hours without food “switches on” autophagy uniformly throughout the body. Nor can we claim that doing so, by itself, reduces the risk of cancer.
Experimental studies of fasting and cancer have generated considerable interest, but research in humans does not yet support recommending fasting as a strategy to prevent or treat cancer.
For someone living with cancer, fasting should never be undertaken without medical advice. Weight loss and malnutrition can compromise general health and the ability to tolerate treatment. Any form of dietary restriction during cancer treatment should be discussed with the medical team responsible for the patient’s care.
Looking Ahead: Understanding when autophagy should be encouraged and when it should be blocked is one of the challenges facing modern oncology. The goal is not simply to switch autophagy on or off, but to learn how to intervene selectively, taking into account the type of tumour and the stage of the disease.
If this knowledge can be translated into effective treatments, it could help to protect healthy cells while making certain tumour cells less able to survive. In the meantime, getting enough sleep, maintaining regular physical activity and following a balanced diet remain sensible ways to preserve health, irrespective of their specific effects on autophagy.
Autophagy ultimately offers us a particularly instructive lesson. A healthy cell must recognise what no longer works, remove it and make use of whatever can still be useful. Research is revealing just how deeply this principle of cellular maintenance is involved in a disease as complex as cancer.
Today’s research is tomorrow’s therapy