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Cancer: How Does It Start? How Does It Spread? How Is It Treated?
An overview of the basic biology involved with cancer and an explanation of conventional treatment methods
Date : 04/02/2012
Author Information
Uploaded by : Evan
Uploaded on : 04/02/2012
Subject : Biology
Cancer cells have various unique features which allow them to continue growing to form a tumour. For example, cancer cells usually do not undergo apoptosis when they mutate and are immune to attempts by other cells to force them to undergo apoptosis. Furthermore cancer cells are deemed to be "immortal". This is because in normal human cells a cell can divide about 50 times before it is forced to undergo apoptosis. This is because every time it undergoes mitosis, small parts at the end of the chromosomes are lost. These small sections are known as telomeres and once a normal cell loses all its telomeres it is forced to undergo apoptosis. Cancer cells gain the ability to synthesise the enzyme telomerase. Telomerase adds telomeres to the ends of the chromosomes, and since the telomeres can never be fully diminished due to their constant recovery, cancer cells can theoretically keep growing and dividing forever. Cancer cells are not subject to normal cell contact inhibition, and so even when they come into contact with other cells, they can continue to divide and replicate whereas normal cells will generally stop dividing when they come into contact with each other. Multiple pathogens exist that can cause cancer. HPV (human papillomavirus) and KSHV (Kaposi's sarcoma Herpes virus) both cause normal cells to become cancerous cells. This is known as transformation. Both HPV and KSHV affect the P53 gene resulting in transformation of the host cells. However, KSHV usually only results in cancer in hosts with weakened immune system e.g. AIDS victims.
When a cell undergoes carcinogenesis which leads to the formation of a tumour, this type of tumour is known as a primary tumour. This tumour can grow to about the size of a few million cells, however, due to the demand of nutrients it cannot grow any more than this at first and so it enters a quiescent phase. However, if some of the cancer cells mutate in such a way that they switch to an angiogenic phenotype then everything changes. The cells begin to secrete various proteins such as angiopoetins, in particular Ang-2, and Vascular endothelial growth factors (VEGFs). These lead to angiogenesis and as blood vessels are incorporated into the tumour, the supply of nutrients increases greatly. This increased supply in nutrients allows the tumour to grow to much larger sizes at which point it becomes detectable. However, these blood vessels do not only supply nutrients to the cells, since cancer cells are able to break away from other nearby cells, some cancer cells can break away and enter the blood stream. In this way the tumour becomes malignant since these cells can be brought to various locations around the body to form new tumours. The process of cancer cells moving from one area of the body to another is known as metastasis. Large primary tumours do not only secrete angiogenesis promoters but they also secrete angiogenesis inhibitors. Experimental proof of this includes the fact that when large tumours are surgically removed from the body, previously undetected tumours start to grow. This shows that the larger tumour was secreting angiogenesis inhibitors which were preventing angiogenesis from occurring in the smaller tumours, however, its surgical removal also takes away the source of angiogenesis inhibitors, therefore the other smaller tumours can promote angiogenesis so that they can get a supply of nutrients so that they are able to leave their quiescent states and begin to divide and grow again In some cases, such as in lung cancer, the cancer cells actually divide and grow towards the blood vessels. In the case of lung cancer there is a basement membrane which the cancerous cells must get past. This is achieved by the secretion of certain proteases by the cancer cells with the necessary mutations. This allows the cancer cells to infiltrate the connective tissue which has a large supply of blood vessels, and most likely, lymph vessels as well, which the cancer cells can use to metastasise. One of the treatments of cancer is chemotherapy. Chemotherapy is the use of specific drugs to damage dividing cells. Since most adult cells have stopped dividing i.e. they are in a G0 or quiescent state, they are not affected by the chemotherapy but the cancer cells (and some cells of the body were cell division occurs normally e.g. in the crypts of the villi in the small intestine) will be damaged by the chemotherapy and will die. Evidently this will have some side effects on the patient. Chemotherapy only works if the cancerous cells are supplied with blood (or are in the blood stream in the case of leukaemia) and as a result small benign tumours may be unaffected by the chemotherapy. Furthermore the chemotherapeutic drugs may not be able to reach the centre of the tumour and also, over time the cancer cells develop resistance to the chemotherapeutic drug being used. Radiotherapy is another form of cancer treatment. It involves the use of radiation and can either be external or internal. External radiotherapy (also known as teletherapy) involves using beams of either photons i.e. x-rays and sometimes Gamma rays, or charged particles i.e. protons, ions or electrons. These are arranged at various angles and concentrated on the tumour so that the majority of the radiation is focused on the tumour so less damage is done to other tissues. Photon beams cause damage to DNA by indirect ionisation which results in single strand breaks in the DNA of the cancer cells. This is achieved by the ionisation of water in the cells resulting in the formation of free radicals which cause single strand breaks in the DNA of the cancer cells. These cannot be repaired by the cancer cells since they have lost their ability to repair themselves as a result this damage is passed on to the next generation of cancer cells when they divide which either slows reproduction or results in the cancer cells dying. However, photon radiotherapy can lead to tumour hypoxia which results in a loss of radiosensitivity in the tumour but this can be treated in various ways such as with certain drugs which increase radiosensitivity of cells in hypoxic conditions such as misonidazole. Protons and charged particles cause direct ionisation and result in double DNA strand breaks which usually result in the cell dying. They also have the advantage that they are not affected by tumour hypoxia because the energy is directly transferred to the DNA. These charged particles also have the advantage that their penetration distance can be altered to ensure maximum radiation reaches the tumour and not the other areas of the body. One form of internal radiotherapy is radioisotope therapy. This only works in certain situations because certain organs take up specific substances more readily than other areas of the body. For example, the thyroid gland is well known for its extreme uptake of iodine. As a result tumours of the thyroid gland may be treated with radioactive iodine. Another form of internal radiotherapy known as brachytherapy involves placing a source of radiation into a tumour. Since the radiation is localised to the tumour other healthy body cells are usually unaffected and as a result high concentrations of radiation can be used. Furthermore, the whole brachytherapy course is usually shorter than the external radiotherapy course and does not require as many visits to the radiotherapy clinic can hence is preferable and more convenient for certain patients. The most successful form of cancer treatment is surgery. It involves the excision of the tumour. Normally a bit of healthy tissue around the edges of the tumour is extracted to ensure that any cancer cells which may not be seen are excised as well. Vaccines (e.g. Gardasil and Cervarix) have been developed against the HPV. However, this is a prophylactic measure since no cure currently exists. KSVH is treated with certain antiviral drugs (e.g. ganciclovir)
In conclusion, cancer starts due to a mutation in a tumour suppressor gene and/or an oncogene which leads to uncontrolled and rapid mitosis. These cancer cells divide and grow to form the primary tumour. This can spread when it switches to an angiogenic phenotype allowing it to incorporate blood vessels, or when it grows towards blood vessels or lymph nodes. This allows the cancer to be transported around the body where it can form new secondary tumours and this process is metastasis. Methods of treatment include chemotherapy, surgery, external or internal radiotherapy.
This resource was uploaded by: Evan