Introduction
Cancer, a
deadly and difficult illness, takes millions of lives globally each year.
Understanding the reason behind cancer at the molecular level is the main focus
today. One important discovery in the field of cancer was Tumor-suppressor
genes.
What Is Tumor Suppressor Genes?
Tumor
suppressor genes can also be classified as anti-oncogenes, which are a class of
genes that prevent the cell from becoming a cancerous cell. Tumor suppressor
genes, in contrast to oncogenes, which encourage cell proliferation and
expansion, operate as defenders of cellular integrity. They prevent
uncontrollable cell division, which is a characteristic of cancer.
The major
role of tumor suppressor genes may be divided into two categories:
1) Cell cycle regulation: Tumor suppressor genes govern the cell
cycle, ensuring that it runs smoothly and precisely. When faults or damage are
discovered, they can pause cell division, giving time for repairs or initiating
programmed cell death (apoptosis) if necessary.
2) DNA repair: Tumor suppressor genes are also involved in DNA repair pathways.
They play a crucial role in fixing genetic abnormalities and damage that occur
in a cell which can possibly pile up to cause cancer one day.
Important Tumor Suppressor Genes
Numerous
tumor suppressor genes have been found, and their roles in cancer prevention
are well established. Some of the most well-known tumor suppressor genes are:
1) TP53 (p53): Known as the "guardian of the genome," the TP53 gene is
critical in preventing the creation of malignant cells. It detects any damage
in the DNA and if found, halts the cell cycle (repair if possible) or undergoes apoptosis.
2) BRCA1 and BRCA2: Mutations raise the risk of breast, ovarian,
and other cancers considerably. They help to repair double-strand breaks in DNA
and keep the genome stable.
3) APC: Colorectal cancer is linked to mutations in the Adenomatous
Polyposis Coli (APC) gene. APC aids in the regulation of cell division in the
gut lining.
4) PTEN: The Phosphatase and Tensin Homolog (PTEN) gene controls cell
development and division. PTEN mutations have been related to a variety of
malignancies, including breast, prostate, and brain cancer.
5) RB1: The Retinoblastoma (RB1) gene aids in cell cycle management by
slowing cell division until it is safe. Mutations in the RB1 gene have been
linked to retinoblastoma and other malignancies.
Tumor Suppression Mechanisms
Tumor
suppressor genes use a variety of ways to perform their protective activities
within cells, including:
1) Cell Cycle Checkpoints: Tumor suppressor genes monitor cell cycle
progression at several checkpoints, such as the G1/S and G2/M transitions. When
DNA damage is discovered, these genes can stop the cell cycle and enable time
for repair.
2) DNA Repair: DNA repair is intimately involved in several tumor suppressor
genes. They help to repair damaged DNA strands, reducing the buildup of
mutations that might lead to cancer.
3) Apoptosis: Tumor suppressor genes can cause apoptosis, or regulated cell
death, in cells with substantial DNA damage or irreversible mutations. This
clears the body of possibly malignant cells.
4) Senescence: It is a condition of irreversible growth inhibition caused by
some tumor suppressor genes. Senescent cells cannot divide and are hence not
malignant.
Tumor Suppressor Genes and
Mutations
The
vulnerability of tumor suppressor genes to alterations is their Achilles' heel.
When these genes are mutated, either to disrupt their normal function or to
render them inactive, the defensive processes they regulate are jeopardised. As
a result, cells may avoid checkpoints, accumulate genetic damage, and avoid
apoptosis or senescence, paving the path for unregulated cell proliferation and
cancer growth.
It should be
noted that tumor suppressor gene mutations can develop via a variety of ways,
including:
1) Inherited Mutations: Some people inherit mutant copies of tumor
suppressor genes, which increases their chance of acquiring particular
malignancies dramatically. BRCA1 and BRCA2 mutations in breast and ovarian
cancer are examples of this.
2) Somatic mutations: Somatic mutation in tumor suppressor genes
can occur over an individual's lifetime as a result of exposure to carcinogens,
radiation, or other reasons. These mutations can happen in certain cells and
lead to the development of cancer.
3) Epigenetic changes: Epigenetic modification such as DNA
methylation and histone abnormalities, can quiet tumor suppressor genes without
changing their DNA sequence. Cancer can be caused through epigenetic silencing.
Implications for Treatment
Understanding
the importance of tumor suppressor genes lead to prevention of cancer and also
possible cures.
1) Gene Therapy: Gene therapy approaches attempt to restore the protective effects
of mutant or inactivated tumor suppressor genes in cancer cells.
2) Small Molecule Inhibitors: To revive the actions of tumor suppressor
genes, small compounds that target particular pathways or proteins are being
produced.
3) Immunotherapy: Immunotherapies such as checkpoint inhibitors, improve the immune
system's capacity to identify and eradicate cancer cells, in part by
reactivating tumour suppressor gene-controlled pathways.
4) Epigenetic Modulators: Drugs that reverse epigenetic silencing of
tumor suppressor genes are being studied as possible cancer therapies.
