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| The specific mutations are frequently in the BRAF, NRAS and KIT oncogenes. Mutations in oncogenes increase the risk of cancer and these three in particular have been linked with melanoma. Sun exposed areas usually have mutations in the BRAF oncogene whereas areas which aren’t exposed to the sun as much show mutations in the KIT oncogene (Takata, 2010). Some other mutations have also been discovered which lead to disruptions to the p16/Rb pathway, cyclin D1 (CCND1) and cyclin dependent kinase 4 (CDK4) which all alter cell cycle progression and cellular senescence (Sauter, 2002; Takata 2010). Proliferation and telomerase mutations also play a role in speeding up the progression of melanoma (Murata, 2007). | The specific mutations are frequently in the BRAF, NRAS and KIT oncogenes. Mutations in oncogenes increase the risk of cancer and these three in particular have been linked with melanoma. Sun exposed areas usually have mutations in the BRAF oncogene whereas areas which aren’t exposed to the sun as much show mutations in the KIT oncogene (Takata, 2010). Some other mutations have also been discovered which lead to disruptions to the p16/Rb pathway, cyclin D1 (CCND1) and cyclin dependent kinase 4 (CDK4) which all alter cell cycle progression and cellular senescence (Sauter, 2002; Takata 2010). Proliferation and telomerase mutations also play a role in speeding up the progression of melanoma (Murata, 2007). | ||
| - | ==== Stages of Skin Cancer ==== | + | ===== Stages of Skin Cancer ===== |
| - | Stage 0 - at this stage melanoma is in situ, meaning that the melanoma cells are only found in the outer layer of the epidermis. In this stage, it is unlikely for melanoma to spread to other parts of the body. | + | **Stage 0** - at this stage melanoma is in situ, meaning that the melanoma cells are only found in the outer layer of the epidermis. In this stage, it is unlikely for melanoma to spread to other parts of the body. |
| - | Stage I - This is the primary melanoma stage, where melanoma cells are only found in the skin. | + | **Stage I** - This is the primary melanoma stage, where melanoma cells are only found in the skin. |
| - Stage IB - subgroup of stage I, depending on the thickness of melanoma and whether or not the pathologist is able to see ulceration under a microscope. | - Stage IB - subgroup of stage I, depending on the thickness of melanoma and whether or not the pathologist is able to see ulceration under a microscope. | ||
| - | Stage II - Melanoma is thicker than in stage I, and extends through the epidermis into the dermis (the inner layer of the skin). In this stage, there is a higher chance of spreading. The stage can be divided into 3 subgroups -- A, b, or C-- depending on the thickness of melanoma and whether there is ulceration. | + | **Stage II** - Melanoma is thicker than in stage I, and extends through the epidermis into the dermis (the inner layer of the skin). In this stage, there is a higher chance of spreading. The stage can be divided into 3 subgroups -- A, B, or C-- depending on the thickness of melanoma and whether there is ulceration. |
| - | Stage III - In this stage, melanoma has spread locally or through the lymphatic system, which is a part of the immune system and drains fluid from the body through tubes or vessels. This stage is also divided into subgroups -- A,B,C or D -- depending on size and number of lymph nodes impacted by melanoma, whether primary tumour has satellite lesion and if ulceration appears under a microscope or not. | + | **Stage III** - In this stage, melanoma has spread locally or through the lymphatic system, which is a part of the immune system and drains fluid from the body through tubes or vessels. This stage is also divided into subgroups -- A,B,C or D -- depending on size and number of lymph nodes impacted by melanoma, whether primary tumour has satellite lesion and if ulceration appears under a microscope or not. |
| - | Stage IV - Melanoma has spread through the bloodstream to other parts of the body (distant locations on the skin, distant lymph nodes or other organs). | + | **Stage IV** - Melanoma has spread through the bloodstream to other parts of the body (distant locations on the skin, distant lymph nodes or other organs). |
| - | - M1a: the cancer only spread to distant skin | + | |
| - | - M1b: the cancer spread to the lung | + | - M1a: the cancer only spread to distant skin. |
| - | - M1c: the cancer spread to any other location that does not involve central nervous system | + | |
| - | - M1d: The cancer has spread to the central nervous system (brain, spinal cord or cerebrospinal fluid) | + | - M1b: the cancer spread to the lung. |
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| + | - M1c: the cancer spread to any other location that does not involve central nervous system. | ||
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| + | - M1d: The cancer has spread to the central nervous system (brain, spinal cord or cerebrospinal fluid). | ||
| ====== Current Treatments, Future Treatments and Implications ====== | ====== Current Treatments, Future Treatments and Implications ====== | ||
| - | **Chemotherapy** | + | === Chemotherapy === |
| - | - Vindesine - The vinca alkaloid vindesine has also been evaluated in the adjuvant treatment of malignant melanoma. In a non-randomised trial, researchers have found a highly significant improvement in disease-free as well as the overall survival in patients treated with vindesine following resection of regional lymph nodes compared with patients followed by observation alone. | + | |
| + | __Vindesine__ - The vinca alkaloid vindesine has also been evaluated in the adjuvant treatment of malignant melanoma. In a non-randomised trial, researchers have found a highly significant improvement in disease-free as well as the overall survival in patients treated with vindesine following resection of regional lymph nodes compared with patients followed by observation alone. | ||
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| + | __Levamisole__ - This is another type of chemotherapy that has been evaluated as an adjuvant treatment following excision of a primary melanoma. In a trial conducted by the National Cancer Institute of Canada, were able to demonstrate a reduction of 29% in both the death rate (p = 0.08) and the recurrence rate (p = 0.09) in a cohort of patients who were randomized to receive adjuvant levamisole as opposed to observation alone. | ||
| - | - Levamisole - This is another type of chemotherapy that has been evaluated as an adjuvant treatment following excision of a primary melanoma. In a trial conducted by the National Cancer Institute of Canada, were able to demonstrate a reduction of 29% in both the death rate (p = 0.08) and the recurrence rate (p = 0.09) in a cohort of patients who were randomized to receive adjuvant levamisole as opposed to observation alone. | + | === Gene Therapy === |
| - | **Gene Therapy** | + | Constitutive activation of certain signal transducer and activator of transcription proteins, including Stat3, has been found in increasing numbers of human cancers. Researchers have found that the levels of activated Stat3 in the B16 tumour cell line are relatively low. Over-expression of a Stat3 Dominant-negative Protein, Stat3b, Induces Cell Death in B16 Tumour Cells in Vitro (Niu et al., 1999). |
| - | - Constitutive activation of certain signal transducer and activator of transcription proteins, including Stat3, has been found in increasing numbers of human cancers. Researchers have found that the levels of activated Stat3 in the B16 tumour cell line are relatively low. Over-expression of a Stat3 Dominant-negative Protein, Stat3b, Induces Cell Death in B16 Tumour Cells in Vitro (Niu et al., 1999). | + | |
