Introduction
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In a world so focused on personal appearance we think about our skin a lot. Facial cleansers, lotions, tanning, wrinkle prevention, are all products developed to make our skin look better. However, we are forgetting the original purpose of our skin, to protect us. Skin is the first line of defense against bacteria and viruses. Skins’ protective barrier prevents dehydration and protects our body from both hot and cold temperatures. For as strong as our skin is it still has a vital weakness, the sun. When the body is exposed to too much UV radiation from the sun, the results can be life threating. Ultraviolet rays can cause damage to your body’s DNA, damaging your cells’ code and leading to cells malfunctioning, and production of cancerous tumors, affecting approximately 1 out of 55 people in the US [1]. Melanoma is actually one of the better-known cancers when it comes to the signaling pathways involved. So far the most understood pathways members are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt.[2]
Melanoma is just one type of skin cancer, which affects the pigment producing cells leading to uncontrolled cell growth, approximately 87,000 new cases will develop over the year [3] . Melanoma is one of the less common skin cancers, but it is still incredibly dangerous because it spreads and can metastasize to other parts of the body such as the lymph nodes, brain, lungs, or liver. Melanoma kills approximately 9,320 people in the United States every year [3]. Skin cancer can affect everyone, but those who have a lot of moles, a weakened immune system, fair completion, or a family history of melanoma are more vulnerable [4]. In recent years there has been a steady increase of about 3-7% of cases of melanoma per year, worldwide [4]. Part of the reason for this increase is our cultural change to seeking out more natural and artificial sun exposure. Tanning beds specifically have been related to a 75% increase in melanoma risk [4]. Currently there is no known cure, the best treatment option we have is prevention. Which is why it so important to be informed of the causes, symptoms, and methods of prevention we can take as individuals who care about our skin.
Melanoma
Andrea Buchholz
Symptoms
When it comes to melanoma early detection is key. It is recommended that one should receive yearly screenings from your dermatologist. Knowing the ABCDE’s of melanoma is important because knowing your body and being able to recognize the difference between normal and abnormal moles can be the difference between a simple removal and having to go through chemotherapy. Often the affected area can be removed if it is still in the early stages (stage I). If treatment isn’t sought soon enough and the risk increases and can even become lethal. Treatment is based on the stage of the cancer. In stage II large amounts of skin may need to be removed, as well as a possible lymph node biopsy. In stage III melanoma, the cancer has reached the lymph nodes and extensive tumor removal as well as lymph node dissection must be performed. Once the cancer has reached stage IV it becomes very difficult to cure, the cancer has already spread to the lymph nodes and other parts of the body. From there, traditional cancer treatments such as chemotherapy, surgery, and biological therapy are used.
Cell Signaling
Melanoma has some of the better understood cancer signaling pathways. While there is still much left to learn, it is generally accepted that there are multiple signaling pathways involved in the development and progression of melanoma. [2] The above diagrams show the two most significant signaling pathways in melanoma. The mitogen-activate protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3k-Akt) pathways are involved in many cellular processes such as cell proliferation, differentiation, development, migration, apoptosis, transformation, cell survival, cell growth, transcription and translation [5]. Mutations in the MAPK pathways are found in more than 50% of melanomas [6], and mutations in the PI3K-Akt pathway are found 30-50% of the time [2]. In normal cell function the MAPK pathway reacts to the binding of growth factor which promotes RAS GTP associations and hydrolyzes GTP and activates the Raf pathway, in cancerous melanoma cells there is a mutation in RAS which inhibits its ability to hydrolyze GTP which makes the NF1 lose its function, leading to uncontrolled continuous DNA transcription.[5] For the PI3k-Akt pathway normally the cell is regulated by PTEN which is the main negative regulator and inhibits Akt activations, without PTEN AKt is over-activated, leading to the whole pathway being over active, resulting in an increase in the production of predates and an increase in cell proliferation, all of which favor melanoma development. [5]
Treatment Options
References
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[1] Coit DG, Andtbacka R, Bichakjian CK, Dilawari RA, Dimaio D, Guild V, et al. Melanoma. J Natl Compr Canc Netw 2009;7:250-275.
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[2] Lopez-Bergami, P., Fitchman, B., & Ronai, Z. (2008). Understanding Signaling Cascades in Melanoma. Photochemistry and Photobiology, 84(2), 289-306. doi:10.1111/j.1751-1097.2007.00254.
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[3] Passarelli, A., Mannavola, F., Stucci, L. S., Tucci, M., & Silvestris, F. (2017). Immune system and melanoma biology: A balance between immunosurveillance and immune escape. Oncotarget, 8(62). doi:10.18632/oncotarget.22190
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[4] Erdei, E., & Torres, S. M. (2010). A new understanding in the epidemiology of melanoma. Expert Review of Anticancer Therapy,10(11), 1811-1823. doi:10.1586/era.10.170
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[5] Dantonio, P., Klein, M., Freire, M. R., Araujo, C., Chiacetti, A., & Correa, R. (2018). Exploring major signaling cascades in melanomagenesis: A rationale route for targetted skin cancer therapy. Bioscience Reports, 38(5). doi:10.1042/bsr20180511
[6] Jasmina Paluncic, Zaklina Kovacevic, Patric J. Jansson, Danuta Kalinowski, Angelika M. Merlot, Michael L.-H. Huang, Hiu Chuen Lok, Sumit Sahni, Darius J.R. Lane, Des R. Richardson,Roads to melanoma: Key pathways and emerging players in melanoma progression and oncogenic signaling,Biochimica et Biophysica Acta (BBA) - Molecular Cell Research,Volume 1863, Issue 4,2016