• Cancer is defined as uncontrolled growth of a group of cells disregarding the normal rule of cell division. Such cells are known as cancer cells.
• Normal cells are under direct supervision and their growth, proliferation and cell division are supervised through signal transduction. However cancer cells develop autonomous mechanism for its growth and proliferation.
• Cancer is diseases which turns the normal cell into cancer cell by the process called carcinogenesis.
• Clinically, there are many types of cancer, but biologically, the origin of cancer is similar, which is due to defect in gene expression.
• There are some factors which are responsible for change of normal cell into cancer cell. Those factors or agents are known as carcinogens.
• It is believed that all cells carry certain cancer producing oncogenes.
• Oncogenes are the genes that are responsible for induction of tumors. Under certain conditions these genes are triggered to multiply rapidly into malignant neoplasm.

Etiological agents that induce cancer:

1. Environmental factors:

• tobacco, smokes, diets, environmental pollutants etc
• Heavy smoking cause lung, oral cavity and oesophagus cancer.
• Excessive intake of alcohol cause liver cancer.

2. Chemical carcinogen:

• Nickel compounds, cadmium, arsenic, nitrosamines, trichloroethylene, arylamines, benzopyrene, aflatoxins, reactive oxygen radicals etc

3. Physical carcinogen:

• UV rays (ultraviolet), ionizing radiation (x-rays and gamma rays)

4. Biological carcinogen:

• Virus:
• Virus has also been associated with various types of cancers. These viruses are called oncoviruses .
• Rous sarcoma virus (RSV) is the first discovered retro-virus causing cancer.
• (Oncovirus); Human papilloma virus (HPV), Epstein-BarrVirus, (EBV), Hepatitis B virus, Herpes virus
• Hepatitis B and C virus is casually related with hepato-cellular carcinoma.
• Cytomegalovirus (CMV) is associated with kaposi’s sarcoma.
• Human papilloma virus (HPV) is a chief suspect of cervix cancer.

• Bacteria; Helicobacter pylori,

5. Endogenous factors:

• Mutations, change in DNA replication, metabolic reactions generating, reactive oxygen radicals, Immune system defects,  Ageing

Cancer pathophysiology

• Regardless of difference in types of cancer histologically and physiologically, there is existence of a common pathophysiological process of malignant tumors or cancer development in the organism.
• The commonly accepted basis of the pathogenesis of cancer is the damage to the genetic
  apparatus of cells (such as mutation, disturbance of gene expression, activation of tumor promoter gene, inactivation of tumor suppressor genes, etc.)
• It is believed that damage to the genetic apparatus of the cell along with inactivation of anti-tumor genes takes place and is essential for the development of malignant tumors. But it should be noted that the inactivation of tumor suppressor gene is one of the natural physiological reactions of the organism, and when this reaction becomes pathophysiological condition of an organism it results in cancer development.

Figure. Pathogenesis of cancer

At the cellular level, the development of cancer is viewed as a multi-step process involving mutation and selection for cells with progressively increasing capacity for proliferation, survival, invasion, and metastasis.

First step: Mutation and tumor initiation

• Genetic alteration leads to mutation in a single cell which results into abnormal proliferation of that cell known as tumor cell.

Second step: Cell proliferation and Tumor progression

• Tumor progression continues as additional mutations occur within cells of the tumor population.
• The mutated cells have some selective advantage over normal cell as such cells shows rapid growth and division. The descendants of a cell bearing such additional mutation will consequently become dominant within the tumor population

Third step: Clonal selection and malignancy

• Cell proliferation of tumor then leads to new clone of tumor cells with increased growth rate or other properties (such as survival, invasion, or metastasis) that confer a selective advantage. The process is called clonal selection.
• Clonal selection continues throughout tumor development, so tumors continuously become more rapid-growing and increasingly malignant.
• For example: In colon cancer, the earliest stage in tumor development is increased proliferation of colon epithelial cells. A clonal selection occurs in which, a single cell within these proliferative cell population give rise to a small benign neoplasm. Further rounds of clonal selection lead to the growth of benign neoplasm with increase in size and proliferative potential resulting in malignant carcinoma. The cancer cells then continue to proliferate and spread through the connective tissues of the colon wall. Eventually the cancer cells penetrate the wall of the colon and invade other abdominal organs, such as the bladder or small intestine. In addition, the cancer cells invade blood and lymphatic vessels, allowing them to metastasize throughout the body.

Fourth step: Metastasis

• Metastasis is a complex process in which cancer cells break away from the primary tumor and circulate through the bloodstream or lymphatic system to other sites in the body.
• At new sites, the cells continue to multiply and eventually form additional tumors comprised of cells that reflect the tissue of origin.
• The ability of tumors, such as pancreatic cancer and uveal (iris, ciliary body, or choroid of eye) cancers, to metastasize contributes greatly to their lethality.
• Many fundamental questions remain about the clonal structures of metastatic tumors, phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, how the tumor disseminates, and the role that the tumor micro-environment plays in the determination of the metastatic site.

Types of cancer

• Abnormal proliferation of any of the different kinds of cells in the body can result in Cancer. So there are more than a hundred different types of cancer varying on their behavior, pathophysiology, site of origin and response to treatment or therapy.
• A tumor can be either benign or malignant.
•  Benign tumor: A tumor that remains confined to its original location, neither invading surrounding normal tissue nor spreading to distant body sites is known as benign tumor. For examples; Skin wart
• Malignant tumor: A tumor which is capable of both invading surrounding normal tissue and spreading (metastasis) throughout the body via the circulatory or lymphatic systems is known as malignant tumor. Only malignant tumors are properly referred to as cancer.
• Pathologically, cancers are classified into three categories: Carcinomas, Sarcomas, Leukemia:

1. Carcinomas:

• This type of cancer arises from epithelial cells or ectodermal tissues lining the internal surface of the various organs.
• For example: breast cancer, lung cancer, skin cancer, brain cancer, cancer of pancreas and mouth, oesophagus, stomach and intestine.

2. Sarcomas:

• These cancers arise from connective and muscular tissue derived from mesoderm.
• For examples: bone tumours, muscle tumours, muscle tumours, cancer of lymph nodes.

3. Lymphomas or Leukemia:

• It is the malignant growth of leucocytes (WBC).
• Persons affected with this cancer show the excessive production of leucocytes (blood cancer) and cancer of bone marrow.
• In addition, brain tumor, kidney tumor and eye tumor is seen in infants and children due to malignant growth of primitive embryonic tissues. Similarly, cervical cancer is common in women and prostate cancer common in men.

Cancer Diagnosis (symptoms of disease)

• The early infection does not show significant symptom. Possible symptoms of cancer are as follows:
• A persistent cough or hoarseness in a smoker.
• A persistent change in digestive and bowel habits.
• Rapid change in the form, appearance and growth of a mole or wart.
• A hard area in the breast.
• Excessive loss of blood during monthly period in women.
• A swelling or sore throat that does not heal easily.
• Unexpected loss of weight.

Cancer Treatment

• Early treatment ensures that the cancer can be controlled. Some of treatments may control cancers.

1. Radiation or Radiotherapy:

• It involves the exposure the cancerous part of the body to high doses of radiation which can destroy rapidly growing cells and shrink tumors.

2. Surgery or  Operation:

• Generally tumor and cancerous cells are surgically removed.

3. Chemotherapy:

• It involves some anticancer drugs to control cancer.
• Chemotherapy drugs are alkalyting agents ( carboplatin, cisplatin, melphalan) and antibiotics ( actinomycin, mythramycin).

4. Hormone therapy:

• Hormone therapy is a treatment that slows or stops the growth of breast and prostate cancers that use hormones to grow.

5. Stem cell transplant:

• Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy.

6. Precision medicine:

• Precision medicine helps doctors select treatments that are most likely to help patients based on a genetic understanding of their disease.

7. Target therapy:

• Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread.

8. Herbal- therapy:

• Certain medicinal plants have anti- cancer property

References:

1. https://www.cancer.gov/about-cancer/treatment/types
2. https://m.scirp.org/papers/56146
3. https://www.illumina.com/content/dam/illumina-marketing/documents/products/research_reviews/cancer_research_review.pdf

Cancer: etiology, pathophysiology, types, diagnosis and treatment

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