Carcinogenesis and Cancer
Carcinogenesis is the creation of a cancer.
Cancer is, ultimately, a disease of genes. Typically, a series of several mutations is required before a cell becomes a cancer cell. We distinguish between oncogenes, which promote cancer when “switched on” by a mutation, and tumor suppressor genes, which prevent cancer unless “switched off” by a mutation. These mutations can have various causes: radiation or chemicals called carcinogens; some inherited predisposition is not uncommon; some viruses that can cause cancer have also been described. Usually, they carry in their genome some oncogene or tumor suppressor inactivating gene. In about 15% of all cancers, viruses seem to play a role. Finally, damage by free radicals, which are a natural by-product of oxygen metabolism, can cause mutations in the DNA.
For most of the cancers, it cannot be told which event was the initial cause. However, with molecular biology, it is possible to characterize the mutations within a tumor, and to a certain extent to predict its behavior. For example, about half of the tumors are deficient in the tumor suppressor gene p53, also known as “the guardian of the genome”. This is associated with poor prospects for the patient, since those tumor cells are unlikely to go into apoptosis (programmed cell death) after they are damaged by therapy. There are more mutations that make a tumor more malignant. Telomerase mutations enable a tumor cell to divide indefinitely. Other mutations enable the tumor to grow new blood vessels to feed it, or to detach from the surrounding tissue, spreading to other parts of the body.
Malignant tumors such as carcinoma or sarcoma, lymphoma or leukemia originate from a cell or a group of cells in a multicellular organism that have several distinct properties:
increased cell division rate
not controllable by growth factors anymore
altered differentiation (specialization) ability
no ability for contact inhibition
ability to invade neighbouring tissue
ability to build metastases
ability to promote blood vessel growth
A cell that degenerates into a tumor cell does usually not acquire all these properties at once, but its daughter cells are selected to build them. This process is called cellular evolution. A first step in the development of a tumor cell is usually a small change in the DNA, often a point mutation, which leads, among other things, to a genetic instability of the cell. The instability increases to a point where the cell loses whole chromosomes, or has double ones. Also, the DNA methylation pattern of the cell changes, activating and deactivating genes more or less at random. Cells that divide at a high rate, such as stem cells, show a higher risk of becoming tumor cells than those which divide less or not at all, for example, neurons. If the initial tumor cell (or group of tumor cells) is not removed by the immune system, it will develop into cancer.
In cellular model systems, cells are exposed to carcinogenic influences (chemicals, radiation). In these systems, the first signs of a cell developing into a tumor cell are :
Immortality. The usual number of cell divisions for a mammalian cell is 50-60 (cell senescence), then it ceases to divide. Tumor cells keep dividing forever.
Altered morphology.
Building of cellular clusters (Foci).
Loss of contact inhibition.
Low or no need for growth factors.
Metastasis
Cancers are capable of spreading through the body by two mechanisms: local invasion and distant metastasis. Invasion refers to the direct migration and penetration by cancer cells into neighboring tissues. Metastasis refers to the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then invade normal tissues elsewhere in the body. Cancer is most deadly when it metastasizes.
Forms of cancer
The term cancer is very broad and covers many different illnesses including:
Bladder cancer
Bone cancer
Brain tumor
Breast cancer
Cervical cancer
Colorectal cancer (includes colon, rectum, anus, and appendix)
Cancer of the esophagus
Hodgkin’s disease
Kidney cancer
Cancer of the larynx
Leukemia
Liver cancer
Lung cancer
Lymphoma
Melanoma
Moles and dysplastic nevi
Multiple myeloma
Muscular Cancer
Non-Hodgkin’s lymphoma
Oral cancer
Ovarian cancer
Cancer of the pancreas
Prostate cancer
Skin cancer
Stomach cancer
Testicular cancer
Teratoma
Thyroid cancer
Cancer of the uterus
Clinical aspects
The field of medicine concerned with the treatment of cancer is oncology.
Cancer has become an important problem with the rise in life expectancy, as the above mentioned mutations become more likely the longer a person lives. Though great progress in treatment has been made, most cancers in advanced stages remain incurable and ultimately fatal.
Treatment of cancer typically involves surgery to remove tumors and nearby lymph nodes to which the cancer may have spread, combined with radiation therapy and/or chemotherapy. The latter two target cells in the body that are rapidly dividing. This includes the cancer cells but also certain healthy ones, which is the reason for the severe side effects of these treatments.
Ahmed El Sayed
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