Introduction
Cancer has
long been a perplexing challenge to healthcare experts and scientists. Although
there are various factors that can lead to cancer, the discovery of oncogenes
has been a significant breakthrough in this field. When these genes undergo
mutation or activation, they can play a crucial role in the initiation and
progression of numerous malignancies.
The Origin of Oncogenes
Oncogenes,
sometimes known as "cancer genes," were discovered in the early
twentieth century when scientists realised that certain retroviruses (viruses
with RNA genomes) could change normal cells into cancer cells. This mutation
was caused by the presence of viral genes, which had the potential to cause
uncontrolled cell development. This game-changing finding cleared the path for
the discovery of oncogenes in the human genome.
Oncogenes can be obtained from a variety of sources
a) Proto-oncogenes: Proto-oncogenes are normal genes found in the human genome that control cell development and division. However, mutations or changes in these genes might cause them to become oncogenes, resulting in aberrant cell growth.
b)Viral oncogenes: Some oncogenes have viral origins and are transmitted by cancer-causing viruses, such as the human papillomavirus (HPV) and the Epstein-Barr virus (EBV). These viruses can insert their genes into the host genome, causing normal cellular functioning to be disrupted.
Oncogene Activation Mechanisms
Oncogene activation is a vital step in cancer formation. Several pathways can activate proto-oncogenes, transforming them into powerful cancer promoters:
1) Point mutations: These are alterations in a single nucleotide inside a proto-oncogene. These mutations can cause the gene to overactivate, resulting in uncontrolled cell division. The most well-known example is the RAS gene mutation in numerous malignancies.
2) Gene amplification: Gene amplification happens when a cell contains numerous copies of a proto-oncogene. This extra genetic material causes the appropriate protein to be overproduced, causing aberrant cell development. The HER2 gene amplification in breast cancer is a good example.
3) Chromosomal translocations: In certain circumstances, chromosomal translocations cause two distinct genes to exchange positions. This can cause a proto-oncogene to fuse with another gene, resulting in the creation of a fusion oncogene. A famous example is the BCR-ABL fusion gene in chronic myeloid leukaemia.
4) Epigenetic alterations: Changes in DNA methylation and histone modifications can promote cancer growth by muting tumor-suppressing genes and activating oncogenes.
Oncogenes' Role in Cancer Progression
Oncogenes are important players in the complicated process of cancer development. Once engaged, they control numerous important elements of cancer development:
1) Cell proliferation: Oncogenes cause unregulated cell division, which results in tumor masses. Uncontrolled growth is a characteristic of cancer.
2) Apoptosis inhibition: Apoptosis, also known as programmed cell death, is a natural process that destroys damaged or defective cells. Oncogenes frequently block apoptosis, allowing cancer cells to avoid death and survive.
3) Tumor Angiogenesis: Oncogenes can encourage the development of new blood vessels, a process known as angiogenesis. This allows the developing tumor to receive a consistent supply of nutrients and oxygen, promoting its growth.
4) Metastasis: The spread of cancer cells to distant sections of the body is referred to as metastasis. Oncogenes can increase cancer cells' capacity to infiltrate adjacent tissues and enter the bloodstream or lymphatic system, allowing them to form secondary tumors.
Cancer Therapy Through Oncogene Targeting
Understanding the critical function of oncogenes in cancer formation has resulted in the development of tailored medicines to inhibit their activity. Because they directly target cancer cells while protecting healthy cells, targeted treatments have significant benefits over standard chemotherapy. Among the prominent approaches are:
1) Tyrosine kinase inhibitors (e.g., imatinib for BCR-ABL in chronic myeloid leukaemia): Small compounds, such as tyrosine kinase inhibitors, can decrease the activity of certain oncogenes and their related signalling pathways.
2) Monoclonal antibodies: Monoclonal antibodies attach to oncogene products, blocking them from supporting cancer development and metastasis (for example, trastuzumab for HER2 in breast cancer).
3) Gene therapy: New gene therapy techniques attempt to repair or replace defective oncogenes with healthy counterparts, thereby "turning off" the oncogene.
4) RNA interference (RNAi)-based treatments: RNAi-based therapies use tiny RNA molecules to mute the expression of certain oncogenes, preventing cancer cell development.
