P53 gene

The TP53 gene (commonly known as p53 ) is one of the most important tumor suppressor genes and is sometimes called the " guardian of the genome ." This gene detects abnormalities in cells and promotes cell repair and apoptosis (cell death). When the p53 protein functions normally, it prevents abnormal cells from multiplying uncontrollably and suppresses the development of cancer.

The role of p53

p53 senses DNA damage when it occurs in cells and regulates the following processes:

1. Cell cycle arrest : When p53 detects DNA damage before a cell divides, it temporarily arrests the cell cycle, allowing DNA repair to occur and preventing the abnormal cell from progressing to the next cell division.
2. Promotes DNA repair : p53 activates proteins that help repair DNA, repairing damage so normal cell division can resume.
3. Induction of apoptosis (cell death) : In the presence of irreparable DNA damage, p53 directs cells into apoptosis (programmed cell death), preventing abnormal cells from multiplying and becoming tumors.
4. Induction of senescence : p53 induces cellular senescence (a state in which cells stop dividing) and suppresses tumor formation by preventing cells that have accumulated damage from further division.

TP53 gene mutations and cancer

Mutations in the TP53 gene are one of the genetic abnormalities seen in a great many types of cancer. When p53 does not function normally, DNA damage in cells is not repaired and proliferation progresses, increasing the likelihood of cancer development. Mutations in TP53 are involved in almost all types of cancer and are a factor that promotes cancer development.

• TP53 mutations are involved in almost all cancers, including breast cancer, lung cancer, colon cancer, liver cancer, pancreatic cancer, prostate cancer, and brain cancer.
• Cancers in which mutations are common : TP53 mutations are particularly common in ovarian , small cell lung , and pancreatic cancers .

TP53-related disorders

Mutations in the TP53 gene are also associated with hereditary cancer syndromes, the most prominent of which is Li-Fraumeni syndrome .

1. Li-Fraumeni Syndrome (LFS)

• Li-Fraumeni syndrome is a syndrome caused by an inherited mutation in the TP53 gene and carries a very high risk of cancer.
• High risk of cancers : Cancers such as breast cancer, osteosarcoma, soft tissue sarcoma, brain tumors, leukemia, and lung cancer may occur at a younger age.
• People with this syndrome have a higher risk of developing several types of cancer than the general population, and if the gene mutation is identified, regular cancer screening is recommended.

p53-targeted therapy

Because TP53 mutations are involved in many cancers, therapeutic approaches targeting p53 are being investigated.

1. Activation of p53 : Reactivating non-mutated p53 may induce apoptosis in cancer cells, and drugs that restore p53 function are being developed.
2. Activation of alternative p53 pathways : In cases where p53 is not functional, methods to activate other tumor suppressor pathways (such as p16) are being investigated.
3. Combination with immunotherapy : Attempts are being made to combine immunotherapy with p53-targeting therapy to prevent cancer cells from evading the immune system and improve the effectiveness of cancer treatment.

Future therapeutic possibilities of p53

• p53 is attracting attention as a target for cancer treatment. In particular, if drugs or treatments can be developed to restore abnormalities in p53 in cancer cells, it is expected that they will be effective in halting the progression of cancer.

summary

TP53 (p53) is an important tumor suppressor gene that senses DNA damage in cells and promotes repair and apoptosis. Mutations in p53 are associated with many cancers, and loss of function of p53 significantly increases the risk of cancer development. Therapies targeting p53 are underway and may play an important role in cancer treatment in the future.