Cancer Treatment: p53, a Tumor Suppressing Gene, Stabilized by Spider Silk

Cancer is one of the terminal diseases we have yet to overcome. Its permanent cure is yet to be found. However, depending on the stage of cancer, remission can be achieved, while in some cases, hospice care is a better option. The diagnosis of cancer is sometimes associated with fear and psychological stress.

Spider Web

Spider Web

Cancer is a disease where cells divide and grow uncontrollably. It can occur in any part of the body. These cancer cells can spread or metastasize to other body parts. However, some mechanisms have been put in place naturally to prevent abnormal cell growth and division. Some of which are the innate and adaptive immune mechanisms. Tumor suppressor genes are part of the innate immune system. They repair damaged DNA, slow down cell division, and can cause apoptosis. An example of a tumor suppressor gene is p53. One of the functions of p53 is gene mutation prevention, which in turn prevents cancer development. However, the body produces only a little amount of p53 and breaks down rapidly the ones produced, its half-life is about 5 to 20 minutes. The reason is that it is a disordered and very large protein. Making this protein more stable will be an approach that is promising in cancer therapy.

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The progress so far

Some studies have shown that p53 protein can be made more stable and potent. However, more studies need to be carried out to find out the body’s response to these new p53 proteins and if administration of large amounts of the proteins will be toxic to the body, thereby determining how it will be used in cancer therapy.

In the trial for developing more stable p53 done in KI’s Department of Biosciences and Nutrition, a small portion of spider silk protein was attached to the human p53 protein. The spider silk gave structure to the disordered sections of p53 as discovered by electron microscopy. The new p53 proteins were more stable than the ordinary p53, with the capability of killing cancer cells. When they were added to cells, large amounts of p53 were produced.

However, there is a need to study the new proteins in detail, how the body sees the spider silk component, and how the cells react to this new p53. This can help in developing cancer vaccines that are mRNA-based.

Some other factors can cause p53 to be more stable. One of these is stress. Ionizing radiation caused DNA double-strand breaks leading to increased p53 in a trial by Kastan et al. Other stressors like Hypoxia, ultraviolet rays, nutrient deprivation, and even oncogenic stimuli also stabilize and increase p53 levels. Furthermore, proteins have been noted to influence p53 stabilization and activation. They include proteins that affect p53 subcellular localization, proteins that in other ways, modify p53, protein kinases, among others.

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Since p53 gene mutations are found in roughly half of the cancer cells, and p53 prevents the development of cancer cells from cells with DNA damage, it is necessary to stabilize and increase p53 levels in cells so this guardian of the genome can have more time to act on cells and reduce cancer cells development.

Clinical significance

Cancer is one of the debilitating diseases that affect lifestyle and quality of life. Finding a permanent cure to it will be a groundbreaking event and give back hope to many people.

This study explores one of the ways to achieve cancer treatment, and possibly a cure. There is a need for more research on the p53 protein so it can be effectively harnessed to perhaps bring an end to the age-long war of humanity with cancer.

Conclusion

In addition to the much research going on to bring a solution, this study offers hope and brings light to the research world on cancer treatment. This study is a bedrock that, if built upon, can bring a lasting solution to one of the terminal diseases that has ravaged humanity, cancer.

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References

A “spindle and thread” mechanism unblocks p53 translation by modulating N-terminal disorder

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