Melanomas and Gene Therapy

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8th Feb 2020 Medical Reference this

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Abstract

Melanomas are a type of cancer that arises from melanocytes that are specialized in pigments cells predominant in the skin. The number of cases worldwide is increasing every year. Where the key factor to prevent and lower incidence of this type of cancer is the early detection. In preliminary stages, malignant melanoma can be cured through surgical procedure, but once it has advanced to metastatic stage, it is almost impossible to treat and does not respond positive to existing therapies. Recent research in cell have provide great advances using Gene Therapy and immunotherapy to treat melanoma, where gene therapy is the ideal for targeting metastatic melanomas.

Keywords: Melanomas, Cancer, Gene Therapy, Genes, Symptoms, factors.

Melanomas and Gene Therapy

The word melanoma comes from the Greek words, Melas, meaning black and Oma means tumor. Melanoma is one of the ten most common and dangerous skin cancers with a steadily increasing incidence. Melanoma occurs when the melanocytes that are the main responsible of producing melanin, suffer a malignant transformation, consequently affecting the production of the endogenous pigments in the epidermis. (Skalnikova, 2017). Malignant melanoma is one of the major problem due to its high occurrence among patients compared with any other type of cancer worldwide. Melanomas are highly metastatic and resilient to chemotherapy and can be formed where there is pigment. Therefore, it is crucial to treat melanomas with an early detection and prevention (Chakraborty, 2017). According to the American Cancer Society (ACS), nearly 92,000 of new melanoma cases are expected to be diagnosed in 2018, taking away almost 10,000 lives, due to the fact that this type of cancer affects not just adults and seniors, but teenagers as well. Melanoma is a very difficult cancer to advert on the skin. It is noteworthy how research has come up with a variety of therapies for melanomas, yet some of them might be more harmful compared to its effectiveness. This leads to seek for better solutions like gene therapy for melanoma skin cancer.  Because it can cure an individual, it also averts diseases through a blood line (Chakraborty, 2017). Therefore, could gene therapy offer clues for new treatments for diseases including melanomas.

Composition of the skin and Symptoms of melanomas

Human skin is composed of two main layers, the outer layer called the epidermis, and the inner one named the dermis. The deeper layer of the epidermis contains the melanocytes responsible for the color of the skin. Whereas the melanoma stars in the melanocytes when the skin is exposed, resulting in the damage and therefore in the abnormal and uncontainable growth of the cell creating a tumor. This can grow deep into the dermis, where some of the risks include invading the lymph nodes, and therefore, speeding entirely through the body. Melanocytes are present outside of the skin, in the eye, meninges and mucosal epithelia, however their process begin in the neural crest (Lo, 2014). This type of cancer is one of the most common found in men and women between the ages of 20 and 40 years, ranked third most common in women and second for men according to AIM at Melanoma Foundation. The melanoma types are based on its appearance on microscope or naked eyed. However, studies have shown that symptoms for most of the types of melanomas non-melanomas are almost the same. The American Cancer Society recommends the ABCDE rule, for recognizing the usual symptoms of melanoma:

  • Asymmetry: sides of the pigment spot or mole do not match.
  • Border: when the borders of a lesion are not regular, examples of irregularities can be blurred, ragged or notched.
  • Color: the pigmented mole contains several colors. Different shades of black, brown, sometimes with patches of other colors like pink, red, white and even blue.
  • Diameter: the spot is larger than 6mm in diameter.
  • Evolving: the mole changes with time the size or color.

A normal mole is usually considered small, should have smooth, symmetrical borders, and an even color. It is very important for people who reach the ages of 20 and above to have a physical diagnosis every year in order to prevent and identify any skin abnormality. Any suspicion of a mole or any other irregular lesion must be seeing by a dermatologist once found. People with high risks of skin problems should visit more than once to the dermatologist and have any abnormal lesion removed and analyzed for cancer (Crowder, 2014).

The most common melanomas are the mucosal melanoma, cutaneous melanoma and uveal melanoma, named after their place of origin in the body. Also, there has be some consideration of the factors that can influence the development of melanoma comparable to the degree of skin pigmentation, hereditary predisposition, as about 10% of melanomas have familial occurrence and the length of skin exposure to Ultraviolet radiation (Yang GB, 2011). Almost 80% of people who suffer from basal cell carcinoma, which is the most common skin cancer but the least malignant, have a higher risk of being diagnosed with melanoma, also the people who have multiple moles or lesions have nearly the same chances. The lesion often occurs on sun exposed areas of the face; it appears as dome shaped nodules that later on develop as an ulcer. This type of cancer is slow growing, and metastasis can occur. The second most common type is squamous cell carcinoma that rises from the keratinocytes of the stratum spinosum. This type of cancer tends to grow quickly and metastasize if it is not removed (Learning, 2018). Crowder states that the people with the highest risks are found in jobs or prolonged exposures coal asphalt, creosote, arsenic compounds, or radium.

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In addition, melanoma skin cancer can be associated with genes. Most of melanoma occurs due to mutations in BRAF gene, which alter the protein causing the cancer. Also, melanomas can change the C-KIT gene that help them grow. Changes in the CDKN2A gene roots some melanomas to run in certain families through their bloodline. Modern treatment therapies have been flourishing; one of them is based on experiments and clinical trials known as “Gene Therapy.” it is an advance type of therapy meant to cure the disease by introducing the correct copy, replacing the defective gene. When a mutation on a specific gene occurs, it will develop as a defective protein, leading to complex diseases such as cancer. Most of the time cancer occurs due to the activation of onco-genes that create malignant tumors due to the inactivation of cancer suppressor genes. Gene therapy could solve this problem by stopping the activation of onco-genes and antisense sequence which block onco-gene translation into mutated protein, by hybridization and creation of a double stranded complementary RNA sequence. Another therapy is known as suicide gene therapy, where a set of trans-gene is introduced into cancerous cell which will cause apoptosis to prevent cancer.

 The cancer can also be treated by immunotherapy, chemotherapy, and surgery. However, there are targeted drugs for specifics genes that can serve as a solution to control the changes in these certain genes (Chakraborty, 2017). Chemotherapy is a general term used for cancer treatment which requires using chemical to kill cancer cells. This type of therapy travels through the bloodstream throughout the body. One of the advantages is the effectiveness on destroying cancer cells. On the other hand, there are some long-term effects since chemotherapy attracts the division of cells, meaning that other cells that are normally dividing could be at risk of being attacked. Another reason is that chemotherapy tends to destroy white blood cell, making the body weak against common diseases. Also, it can cause infertility to both men and women depending of the type of chemotherapy. Radiation therapy implement high energy rays to kill cancer cells. However, this type of therapy does not cure cancer, but instead helps to shrink the tumor. It also has some negative aspect, such as lack of energy, hair loss, nausea, vomit, and loss of appetite.

Even though melanoma is the least common skin cancer, with only 1% of deaths on all reported cases, it is the deadliest of any skin disease according to AIM at melanoma foundation. The key to survive melanoma is early detection (Learning, 2018). By the end of 2018 less than 4,000 women and 6,000 men are expected to die in the U.S. According to the American Cancer Society. Advances in the understanding of genetics related to melanomas could prevent and improve strategies that will perhaps evolve over the next decades. Gene therapy has emerged as a potential alternative treatment due to its clinical success and safety developments in the field of gene transfer method. Gene therapy shows promising results by shrinking the tumor and prolonging a patient’s life. Yet, prevention and early detection remains the primary goal against melanomas (Sotomayor, 2002). Where the most important key factor for skin cancer is due to UV exposure, damaging the DNA bases. In other cases, irritation of the skin by infections, physical trauma and chemicals tend to be a predisposing factor. Survival rates decline with increasing thickness of the melanoma, and the degree of involvement of the lymph nodes and level of metastasis (Learning, 2018). The mortality rate for melanoma is 100,000 people per year, increasing at slower step and has been stable over the past 10 years. Therefore, prevention and early detection rely on the understanding and explanation to the vulnerable population, the need of protection from UVR in order to achieve an optimal prevention of melanoma rates (Lo, 2014). While referring to gene therapy for melanoma or specific diseases it means that certain genes are associated with events that are responsible for the disease and should be targeted. Therefore, those genes responsible for melanoma must be discovered and studied in order to apply a therapy for making it a complex but doable process.

References

Abstract

Melanomas are a type of cancer that arises from melanocytes that are specialized in pigments cells predominant in the skin. The number of cases worldwide is increasing every year. Where the key factor to prevent and lower incidence of this type of cancer is the early detection. In preliminary stages, malignant melanoma can be cured through surgical procedure, but once it has advanced to metastatic stage, it is almost impossible to treat and does not respond positive to existing therapies. Recent research in cell have provide great advances using Gene Therapy and immunotherapy to treat melanoma, where gene therapy is the ideal for targeting metastatic melanomas.

Keywords: Melanomas, Cancer, Gene Therapy, Genes, Symptoms, factors.

Melanomas and Gene Therapy

The word melanoma comes from the Greek words, Melas, meaning black and Oma means tumor. Melanoma is one of the ten most common and dangerous skin cancers with a steadily increasing incidence. Melanoma occurs when the melanocytes that are the main responsible of producing melanin, suffer a malignant transformation, consequently affecting the production of the endogenous pigments in the epidermis. (Skalnikova, 2017). Malignant melanoma is one of the major problem due to its high occurrence among patients compared with any other type of cancer worldwide. Melanomas are highly metastatic and resilient to chemotherapy and can be formed where there is pigment. Therefore, it is crucial to treat melanomas with an early detection and prevention (Chakraborty, 2017). According to the American Cancer Society (ACS), nearly 92,000 of new melanoma cases are expected to be diagnosed in 2018, taking away almost 10,000 lives, due to the fact that this type of cancer affects not just adults and seniors, but teenagers as well. Melanoma is a very difficult cancer to advert on the skin. It is noteworthy how research has come up with a variety of therapies for melanomas, yet some of them might be more harmful compared to its effectiveness. This leads to seek for better solutions like gene therapy for melanoma skin cancer.  Because it can cure an individual, it also averts diseases through a blood line (Chakraborty, 2017). Therefore, could gene therapy offer clues for new treatments for diseases including melanomas.

Composition of the skin and Symptoms of melanomas

Human skin is composed of two main layers, the outer layer called the epidermis, and the inner one named the dermis. The deeper layer of the epidermis contains the melanocytes responsible for the color of the skin. Whereas the melanoma stars in the melanocytes when the skin is exposed, resulting in the damage and therefore in the abnormal and uncontainable growth of the cell creating a tumor. This can grow deep into the dermis, where some of the risks include invading the lymph nodes, and therefore, speeding entirely through the body. Melanocytes are present outside of the skin, in the eye, meninges and mucosal epithelia, however their process begin in the neural crest (Lo, 2014). This type of cancer is one of the most common found in men and women between the ages of 20 and 40 years, ranked third most common in women and second for men according to AIM at Melanoma Foundation. The melanoma types are based on its appearance on microscope or naked eyed. However, studies have shown that symptoms for most of the types of melanomas non-melanomas are almost the same. The American Cancer Society recommends the ABCDE rule, for recognizing the usual symptoms of melanoma:

  • Asymmetry: sides of the pigment spot or mole do not match.
  • Border: when the borders of a lesion are not regular, examples of irregularities can be blurred, ragged or notched.
  • Color: the pigmented mole contains several colors. Different shades of black, brown, sometimes with patches of other colors like pink, red, white and even blue.
  • Diameter: the spot is larger than 6mm in diameter.
  • Evolving: the mole changes with time the size or color.

A normal mole is usually considered small, should have smooth, symmetrical borders, and an even color. It is very important for people who reach the ages of 20 and above to have a physical diagnosis every year in order to prevent and identify any skin abnormality. Any suspicion of a mole or any other irregular lesion must be seeing by a dermatologist once found. People with high risks of skin problems should visit more than once to the dermatologist and have any abnormal lesion removed and analyzed for cancer (Crowder, 2014).

The most common melanomas are the mucosal melanoma, cutaneous melanoma and uveal melanoma, named after their place of origin in the body. Also, there has be some consideration of the factors that can influence the development of melanoma comparable to the degree of skin pigmentation, hereditary predisposition, as about 10% of melanomas have familial occurrence and the length of skin exposure to Ultraviolet radiation (Yang GB, 2011). Almost 80% of people who suffer from basal cell carcinoma, which is the most common skin cancer but the least malignant, have a higher risk of being diagnosed with melanoma, also the people who have multiple moles or lesions have nearly the same chances. The lesion often occurs on sun exposed areas of the face; it appears as dome shaped nodules that later on develop as an ulcer. This type of cancer is slow growing, and metastasis can occur. The second most common type is squamous cell carcinoma that rises from the keratinocytes of the stratum spinosum. This type of cancer tends to grow quickly and metastasize if it is not removed (Learning, 2018). Crowder states that the people with the highest risks are found in jobs or prolonged exposures coal asphalt, creosote, arsenic compounds, or radium.

In addition, melanoma skin cancer can be associated with genes. Most of melanoma occurs due to mutations in BRAF gene, which alter the protein causing the cancer. Also, melanomas can change the C-KIT gene that help them grow. Changes in the CDKN2A gene roots some melanomas to run in certain families through their bloodline. Modern treatment therapies have been flourishing; one of them is based on experiments and clinical trials known as “Gene Therapy.” it is an advance type of therapy meant to cure the disease by introducing the correct copy, replacing the defective gene. When a mutation on a specific gene occurs, it will develop as a defective protein, leading to complex diseases such as cancer. Most of the time cancer occurs due to the activation of onco-genes that create malignant tumors due to the inactivation of cancer suppressor genes. Gene therapy could solve this problem by stopping the activation of onco-genes and antisense sequence which block onco-gene translation into mutated protein, by hybridization and creation of a double stranded complementary RNA sequence. Another therapy is known as suicide gene therapy, where a set of trans-gene is introduced into cancerous cell which will cause apoptosis to prevent cancer.

 The cancer can also be treated by immunotherapy, chemotherapy, and surgery. However, there are targeted drugs for specifics genes that can serve as a solution to control the changes in these certain genes (Chakraborty, 2017). Chemotherapy is a general term used for cancer treatment which requires using chemical to kill cancer cells. This type of therapy travels through the bloodstream throughout the body. One of the advantages is the effectiveness on destroying cancer cells. On the other hand, there are some long-term effects since chemotherapy attracts the division of cells, meaning that other cells that are normally dividing could be at risk of being attacked. Another reason is that chemotherapy tends to destroy white blood cell, making the body weak against common diseases. Also, it can cause infertility to both men and women depending of the type of chemotherapy. Radiation therapy implement high energy rays to kill cancer cells. However, this type of therapy does not cure cancer, but instead helps to shrink the tumor. It also has some negative aspect, such as lack of energy, hair loss, nausea, vomit, and loss of appetite.

Even though melanoma is the least common skin cancer, with only 1% of deaths on all reported cases, it is the deadliest of any skin disease according to AIM at melanoma foundation. The key to survive melanoma is early detection (Learning, 2018). By the end of 2018 less than 4,000 women and 6,000 men are expected to die in the U.S. According to the American Cancer Society. Advances in the understanding of genetics related to melanomas could prevent and improve strategies that will perhaps evolve over the next decades. Gene therapy has emerged as a potential alternative treatment due to its clinical success and safety developments in the field of gene transfer method. Gene therapy shows promising results by shrinking the tumor and prolonging a patient’s life. Yet, prevention and early detection remains the primary goal against melanomas (Sotomayor, 2002). Where the most important key factor for skin cancer is due to UV exposure, damaging the DNA bases. In other cases, irritation of the skin by infections, physical trauma and chemicals tend to be a predisposing factor. Survival rates decline with increasing thickness of the melanoma, and the degree of involvement of the lymph nodes and level of metastasis (Learning, 2018). The mortality rate for melanoma is 100,000 people per year, increasing at slower step and has been stable over the past 10 years. Therefore, prevention and early detection rely on the understanding and explanation to the vulnerable population, the need of protection from UVR in order to achieve an optimal prevention of melanoma rates (Lo, 2014). While referring to gene therapy for melanoma or specific diseases it means that certain genes are associated with events that are responsible for the disease and should be targeted. Therefore, those genes responsible for melanoma must be discovered and studied in order to apply a therapy for making it a complex but doable process.

References

  • Chakraborty O, Mukherjee A and Roy P. Gene Therapy for Treatment of Melanoma Cancer. Ann Appl Microbiol Biotechnol J. 2017; 1(1): 1002.
  • Crowder, Charlotte, M. P. H. ..ELS. “Melanomas.” Salem Press Encyclopedia of Health, 2014. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&AuthType=ip,sso&db=ers&AN=94462256&site=eds-live&custid=swtexas.
  • Lo, J. A., & Fisher, D. E. (2014). The melanoma revolution: from UV carcinogenesis to a new era in therapeutics. Science (New York, N.Y.)346(6212), 945-9.
  • “Melanoma Skin Cancer.” American Cancer Society, 2018, www.cancer.org/cancer/melanoma-skin-cancer.html. Accessed 22 Oct. 2018.
  • Melanoma Stats, Facts, and Figures. (2014). Retrieved November 15, 2018, from https://www.aimatmelanoma.org/about-melanoma/melanoma-stats-facts-and-figures/
  • Learning, P. (2018). Anatomy & Physiology I. Pearson Learning Solutions.
  • Signs and Symptoms of Melanoma Skin Cancer. (n.d.). Retrieved November 15, 2018, from https://www.cancer.org/cancer/melanoma-skin-cancer/detection-diagnosis-staging/signs-and-symptoms.html
  • Sotomayor MG, Yu H, Antonia S, Sotomayor EM, Pardoll DM. Advances in gene therapy for malignant melanoma. Cancer Control. 2002; 9: 39-48.
  • Skalnikova, Helena Kupcova, et al. “Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research.” International Journal of Molecular Sciences, vol. 18, no. 12, Dec. 2017, pp. 1–32. EBSCOhost, doi:10.3390/ijms18122697.
  • Yang GB, Barnholtz-Sloan JS, Chen Y, Bordeaux JS. Risk and Survival of Cutaneous Melanoma Diagnosed Subsequent to a Previous Cancer. Arch Dermatol. 2011;147(12):1395–1402. doi:10.1001/archdermatol.2011.1133

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