Multistep Carcinogenesis - Pathogenetic Mechanisms and Therapy

Introduction:

Cancer is a chronic health disease. Cancerous cells are the consequence of uncontrolled cell division. The genes responsible for average cell growth have defects resulting in the formation of cancerous cells from normal cells. Apart from genes, carcinogens and radiation can also cause cancer. Cancerous changes can be observed at the cellular, genetic and epigenetic levels.

What Is Carcinogenesis?

Carcinogenesis is the formation of cancer, where normal cells are converted into cancerous cells. Cancer cells arise from a typical single diploid cell. Cancer is a multistage process subject to metabolic and behavioral changes, leading to multiplication. A cancerous cell can change DNA (deoxyribonucleic acid) sequence. DNA consists of many genes. An abnormal gene in DNA can convert a normal cell to a cancerous cell. The mutated genes in a cancerous cell are involved in three to ten genetic events.

What Is Multistep Carcinogenesis?

Carcinogenesis is a multistep process involving multiple genes. Most multistep carcinogenesis processes involve genetic or epigenetic alterations of multiple or independent genes. Protooncogenes are activated in carcinogenesis and help multiply cancerous cells, cellular growth, and differentiation. Tumor suppressor genes are inactivated and usually help inhibit cell division, reducing or suppressing unusual changes that usually occur in the cells. There are three stages in carcinogenesis. They include initiation, promotion, and progression.

• Tumor Initiation: The early concept suggests that the first changes are irreversible. Later studies on cancer involving the lung and colon proved that stable phenotype changes are the first event in carcinogenesis. DNA methylation in the genes can transcriptionally kill tumor suppressor genes. For mutations to occur, they should be present in cells that proliferate and survive the organism's life. A chemical carcinogen can cause a genetic change by changing the molecular structure of DNA, leading to mutation during DNA synthesis.

• Tumor Promotion: In tumor promotion, the initiated cells multiply and promote. This stage includes the clonal increase of initiated cells. The accumulation rate is directly proportional to the rate of cell division. So the initiated cells will produce a large number of cells that are at risk of malignant transformation. These tumor promoters are characterized by their ability to reduce their initial tumor-forming period after exposure to the tumor initiator or to increase the formation.

• Tumor Progression: This stage consists of the malignant transformation of the accumulated cells. The malignant cell phenotype becomes more aggressive in this stage. This stage is also characterized by metastasis and invasion of the tumor to other parts of the body. There will be uncontrolled growth. Changes, including genetic and epigenetic genes, can occur. There will be activation of protooncogenes and inactivation of tumor suppressor genes.

Cancer arises after a single cell has accumulated a series of genetic alterations. These alterations result from somatic mutation, defined as genetic, epigenetic, or chromosomal alterations. Carcinogens increase cancer risk by directly or indirectly increasing the probability of somatic mutations.

What Are the Causes of Cancer?

• There are several causes of cancer, but certain people develop cancer because they do not have a group of oncogenic mutations.

• The initial cause of cancer is complicated to find out.

• DNA damage is considered to be the primary cause of cancer.

• Cancers are usually non-hereditary.

• Exogenous and endogenous agents can cause cancer.

• Exogenous agents like tobacco, smoke, and radon gas cause DNA damage and result in lung cancer.

• Men who smoke tobacco is 14 times more prone to develop lung cancer than a person who is a non-smoker.

• Exposure to ultraviolet (UV) light can cause melanoma (skin cancer).

• Cancer can also be caused by endogenous, that is, substances that are produced inside the body.

• Endogenous agents like diet-related (bile acids), macrophages, and neutrophils and exogenous agents like smoke, radiation, metals, virus, and other genotoxins result in DNA damage.

• Epigenetic alteration results in remodeling DNA repair genes which cause DNA repair deficiency. So there is a significant increase in unrepaired damage and a considerable increase in somatic mutations and stable phenotype alterations resulting in altered field defects and cancer.

What Are the Diagnosis of Cancer?

There are different types of diagnostic methods. They include:

• Physical Examination: In this method, doctors feel lumps and check for color changes or any enlargement of an organ.

• Laboratory Tests: Usually, urine and blood test are done. In the case of leukemia, a complete blood count shows an abnormal number of white blood cells (WBC).

• Imaging Tests: Magnetic resonance imaging (MRI) uses strong magnetic fields and radio waves to produce a detailed view of soft tissues. Computed tomography (CT) uses a combination of x-rays and computer technology to produce cross-sectional slices of hard tissues, positron emission tomography (PET), and the use of radioactive drugs to differentiate between normal and abnormal metabolic activities. Ultrasound and X-rays are also used.

• Biopsy: Doctors collect a sample of cells. The biopsy procedure depends on the type of cancer and the location. Sometimes, a biopsy is the most definitive method to find out about cancer. After taking a biopsy, it is viewed under a microscope. Normal cells will appear uniformly organized and have similar sizes, but in the case of cancer cells, they will be less organized and have different sizes.

What Are the Treatment for Cancer?

• Surgical Therapy: The final goal of cancer treatment is to remove the entire cancerous cells.

• Chemotherapy: Usage of drugs to kill cancerous cells.

• Radiation Therapy: Usage of high energy beams to kill cancerous cells. Radiation treatment can be of two types. They are external beam radiation (outside the body) and brachytherapy (placed inside the body).

• Bone Marrow Transplant: It is also called a stem cell transplant. Bone marrow is the inner material of the bone which produces blood cells. A transplant can be the individual's cells or can be from the donor.

• Immunotherapy: Another name is biological therapy. Immunotherapy uses the immune system to treat cancer. Sometimes immune systems do not recognize cancerous cells. In immunotherapy, cancer cells are identified and fight it.

• Hormone Therapy: Removing or blocking some hormones from the body can prevent the cells from growing, for example, in prostate and breast cancer cases.

• Targeted Drug Therapy: These focus on specific abnormalities.

• Clinical Trials: These are studies to discover new methods of treating cancers.

Conclusion:

Cancer is one of the fatal diseases. The latency period of cancer is high. So it will be difficult for people to find and diagnose cancer at an early stage. Early-stage cancers are significantly less aggressive than late-stage cancers. Knowing the genes which cause cancer and understanding their mechanism of activation and inactivation will give an idea of the development of neoplasm.