One of the body’s most regulated catabolic processes is Autophagy. Autophagy is a natural body process in which cells recycle their constituents by simply transferring them into lysosomes.
The significant role of autophagy is long recognized. There are various studies which have clearly demonstrated a range of pathophysiological and physiological roles of autophagy in cells. However, it is known to have a more paradoxical role in cancer. That is, acting both as a tumor promoter as well as a tumor suppressor.
In other words, autophagy may exert different results in terms of cancer therapy. This may increase the sensitivity to radiations and chemotherapeutic drugs or cause resistance. This indicates that the process of autophagy may provide new ways for the enhancement of the effects of radiation and antitumor drugs.
Autophagy for Cancer Treatment
When we talk about autophagy, cancer is the first associated disease. However, the role of autophagy and the molecular mechanism is not yet defined clearly. It is even paradoxical. In the early stages, the results of autophagy are more as a tumor suppressor. This means enabling cells to abandon damaged contents of the cell, decreasing DNA and ROS damage.
However, in the advanced tumor development stages, autophagy may assist cancer cells to even survive the low-oxygen, low-nutrients circumstances. That is, the process rather acts as a tumor promoter. In actual, a tumor cell’s dependency on autophagy is quite variable. For instance, in basal circumstances, which may also include increased nutrients conditions, pancreatic cancer or similar tumor models show increased levels of autophagy.
Indeed, the role of autophagy in response to various cancer therapies is still recognized. This is because most of the cancer therapies inflict severe stress including cell damage, which induces cell death. However, the results of therapy-induced autophagy in cancer cells work as a double-edged sword. This further depends on the cancer type, the disease’s stage in terms of progression and the duration and type of autophagy.
Indeed, many studies concluded that increased autophagy may lead to resistance to both radiotherapy and chemotherapy. On the other hand, some studies show that various anticancer drugs encourage cell death in cancer cells.
The fact that many clinically approved anticancer strategies that are being used currently induce autophagy, makes the understanding of the functional role of this process within a particular cancer context a lot more relevant. Moreover, this could give some new ways for the enhancement of radiation effects and antitumor drugs.
Autophagy as a Cytoprotective Mechanism
Traditionally, the process is seen as a more pro-survival process. Different studies show that it can result in various outcomes. For now, there are four distinct and functional forms associated with Autophagy.
- Cytoprotective – In this form, cells die as a result of autophagy inhibition
- Cytotoxic – In this form, the induction of autophagy results in either cell death or in case of cell survival, the results come in the form of blockage
- Cytostatic – When the result of autophagy induction is cell growth arrest
- Non-protective – When there are no effects of autophagy for cell growth once it is blocked.
However, all of these forms are distinctive on the basis of functional characteristics, having similar biochemical, morphologic or molecular profiles.