Cancer Therapies

Autophagy and Fasting – The scientific rationale to prevent cancers

Cancer is one of the leading causes of death worldwide. Though dramatic new therapy options exist even for advanced cancers, the diagnosis of cancer is associated with a high degree of morbidity and mortality. Therefore, preventive strategies for cancer are always a topic for research.

The term autophagy is derived from the Greek term for “self-eating” that helps cells survive stress. Autophagy is a natural process that occurs at a cellular level in the body for the degradation and elimination of abnormal proteins and damaged organelles in stressful conditions as a response to starvation, and cell death.

Autophagy involves the formation of a double-membraned vesicle, which covers the cytoplasm and organelles and then fuses with lysosomes(organelles that destroy cells), resulting in the degradation of the contents of the vesicle.

In 2016, Japanese scientist Yoshinori Ohsumi won the Nobel Prize for his discovery of mechanisms of autophagy. His research established the fact that autophagy provided protection against infections, severe inflammations, and also prolonged lifespan. This phenomenon has been observed in cancers, more so in the liver, when loss of autophagy in the liver creates a toxic environment producing chronic inflammation and cell death of normal liver cells thereby leading to liver cancer.

Autophagy in cancers appears to have a complex dual role. Tumor cell growth can be limited by reducing cancer formation or other damage caused by reactive oxygen species (oxidants).The process of autophagy may, thus directly kill developing tumor cells and act as a prevention strategy for tumor progression.

However, studies have also indicated a contradictory role for autophagy in cancer. As mentioned, autophagy also allows a cell to respond to changing environmental conditions, such as in conditions of starvation. When nutrients are deprived, autophagy is greatly increased, allowing the cell to degrade proteins and organelles and thus obtain a source of amino acids, fatty acids, and nucleotides, which would not be available otherwise. This protective role through autophagy allows cells to survive during starvation. Therefore, when tumor cells are deprived of growth/survival factors an increase in autophagy occurs that prevents the cells from dying.

Thus, when tumor cells are starved, autophagy stops them from dying by inhibiting apoptosis. In a tumor, this means that autophagy could potentially also keep tumor cells alive when limited nutrients and hypoxia(low oxygen levels) become prevalent.

Consequently, increased autophagy would promote the growth of solid tumors, whereas reduced autophagy might provide a useful way to limit tumor growth, since autophagy deficiency causes oxidative stress, activation of the DNA damage response, and cell death.

Taken together, these data suggest that autophagy can both stimulate and prevent cancer depending on the context. But for cancer prevention, autophagy inhibits tumor generation through the regulation of reactive oxygen species (ROS). This explains why many anticancer therapies focus on strategies to regulate autophagy, to promote cancer cell death.

The clear role of autophagy for patients with cancer still needs to be defined with larger clinical studies.

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