What Is the Function of A Tumor Suppressor Gene?

What is the function of tumor suppressor genes?

The function of tumor suppressor genes includes the following:

• Detect and repair damage or copying errors in the DNA during replication.
• If DNA damage cannot be repaired, stop further cell growth and division, and initiate apoptosis.
• Stop the cells from proliferating by a process known as contact inhibition. Contact inhibition makes cells stop dividing once they fill up their natural space and come into contact with other cells.
• Inhibit cell migration and metastasis.

What are the targeted therapies for enhancing tumor suppression?

Targeted therapies for enhancing tumor suppression activity involve identification of the specific tumor suppressor genes that are inactivated, and activating them with targeted medication. Therapies targeting activation of tumor suppression are all small molecule drugs. Cancer cells can, however, develop resistance to targeted medications.

Following are the targeted therapies for enhancing tumor suppression:

DNMT inhibitors

DNA methyl transferase (DNMT) is an enzyme that catalyzes a process known as DNA methylation. DNA methylation is the addition of a methyl molecule to specific portions in the DNA, which silences the gene activity in those portions. DNMT inhibitors block the DNMT enzyme and activate the silenced tumor suppressor genes in the cancer cells.

Methylation of tumor suppressor genes is a necessary, normal and reversible process during the cell growth and division phase. The tumor suppressor genes in a normal cell are activated if there is damage to the DNA, or after the cellular division process is completed. In cancer cells the tumor suppressor gene remains inactivated.

The FDA has approved two DNMT inhibitors for treatment of a group of cancers known as myelodysplastic syndrome (MDS) which can develop into acute myeloid leukemia (AML)

HDAC inhibitors

Histone deacetylase (HDAC) is an enzyme that plays a regulatory role in gene transcription (copying of a gene’s DNA), cell growth, survival and proliferation. HDAC inhibitors block HDAC enzyme and activate the tumor suppressor genes.

Histones are proteins that form a supportive structure to the DNA strands, which are coiled around them. HDACs and histone acetyltransferases (HATs) are two enzymes which work together to modulate the cell mechanisms that replicate DNA and repair damaged DNA.

HATs add an acetyl molecule to the histone, which activates the tumor suppressor gene, while HDACs reverse the process making the histone inaccessible for repair by the tumor suppressors.

Many targeted therapies are in different stages of trials and the FDA has approved one HDAC inhibitor as a third-line therapy:

• Vorinostat for the treatment of advanced cutaneous T-cell lymphoma (CTCL)

Vorinostat is currently in clinical trial for the treatment of two other cancers:

Many combination therapies with both DNMT and HDAC inhibitors are in development because the two processes work together to inactivate the tumor suppressor genes.

P53-HDM2 inhibitors

P53 is a tumor suppressor gene that plays a crucial role in controlling cell division and death. HDM2 is a protein that suppresses P53 gene’s activity. Therapies inhibiting HDM2 are in early phases of trials.