Comprehensive Assessment of Therapeutic Efficacy in Melanoma Treatment

This report provides a comprehensive overview of malignant melanoma, the most aggressive form of skin cancer, and its treatment options. It delves into the efficacy of various therapeutic approaches, including Sulforaphane, Temozolomide, Vemurafenib, and Dabrafenib, analyzing their mechanisms of action and advantages in combating melanoma. The report explores the different stages of melanoma and the corresponding treatment strategies, such as surgery, chemotherapy, and targeted therapies. It also examines the potential benefits of Sulforaphane, a natural compound, in balancing hormones, aiding weight loss, protecting the liver and kidneys, and improving diabetes, and supporting mitochondrial functionalities. Furthermore, the report highlights the significance of Temozolomide, Vemurafenib, and Dabrafenib in the treatment of metastatic melanoma, emphasizing their role in DNA methylation, BRAF-mutated melanoma, and the introduction of MEK and BRAF inhibitors. The study aims to assess the effectiveness of these treatments on human malignant melanoma and normal keratinocyte cell lines, investigating effective concentrations, therapeutic combinations, and the comparative efficacy of natural and chemical compounds. The report concludes with a discussion of the study's hypotheses and methodologies, including the use of spectrophotometric techniques for cell viability evaluation.

ASSESSING THERAPEUTIC EFFICACY IN THE TREATMENT OF MALIGNANT MELANOMA 1
ASSESSING THERAPEUTIC EFFICACY IN THE TREATMENT OF MALIGNANT MELANOMA
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Malignant Melanoma Overview
Malignant melanoma is the most aggressive form of skin cancer and is responsible for
over 70 percent of skin cancer deaths. It is a metastatic skin cancer that has its origin traced in
the epidermis cells. It is characterized by pigment-producing cells known as melanocytes which
becomes cancerous with time through their fast growth and multiplication. Research studies have
it that ultraviolet (UV) radiations are the major risk factor for this disease but the manner in
which UV rays stimulate these cancerous cell transformation has remained a dilemma. Mainly,
melanoma affects men as compared women and can develop in any body part. Also, light-
skinned people have high chances of developing melanoma compared to dark-skinned people. Its
signs and symptoms come into limelight mainly after the age 50 years although it can also appear
at any other age depending on the victim’s skin immunity (Svedman et al, 2016, p.109).
Melanoma Skin Cancer Treatment literature review
Research has shown that treatment of Malignant Melanoma depends on the stage of the
disease and its location as well as the victim's overall health status. For instance, Svedman et al
(2016) in their research presents the different stages of Malignant Melanoma treatment. At stage
0, this disease is not yet grown deeper than the top layer (epidermis) and is usually treated
through skin surgery. The approach removes the melanoma and the small normal skin margin
around it. Some of the doctors, however, prefer using an Imiquimod cream or a radiation therapy
instead of the surgery (Dreyer et al, 2016, p.246). At stage 1, the disease is already deep in the
skin and therefore calls for a wide excision during the surgery in order to locate melanoma and
remove it . At this stage, some doctors may prefer sentinel lymph node biopsy especially if the

ASSESSING THERAPEUTIC EFFICACY IN THE TREATMENT OF MALIGNANT MELANOMA 3
disease has spread into lymph nodes. At the third stage, wide excision surgery just like in the
first stage is adopted as the main treatment although some doctors may prefer sentinel lymph
node biopsy, especially if already spread into lymph nodes. At stage III, cancers are usually at
the extent of lymph nodes and surgical treatment, therefore, requires some wide excision to
remove the primary tumor along with the lymph node dissection. Finally, at stage IV is when
melanomas are deemed hard to cure because they have spread widely to lymph nodes at distant
or the other parts of the body. Skin tumors and the enlarged nodes can, therefore, be removed
through surgery or radiation therapy (Esteva et al, 2017, p.115).
Efficacy of Sulforaphane in Treatment of Malignant Melanoma
Sulforaphane is a type of isothiocyanate existing in cruciferous vegetables especially in
broccoli sprouts and fruits (Garbe et al, 2016, p.201). Its effectiveness as a chemoprotective
agent in genetic models, carcinogen-induced cancer models and xenograft models of cancer has
drawn the researcher’s attention in the fight against Malignant Melanoma (Pilgrim et al, 2014,
p.320). Early research has focused on its “blocking ability” of through Phase 2 enzyme induction
and inhibition of the enzymes which are involved in the carcinogen activation process. SFN has
also proved to offer protection against the development of tumors during “post-initiation” stages.
Also, its suppression impacts, including the apoptosis induction and cell cycle arrest have made
it an effective approach in the fight against Malignant Melanoma. Sulforaphane has proved to be
efficacy as a chemoprevention agent because of its bioavailability, metabolism, and distribution.
Advantages of Sulforaphane

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Rather than its ability in the treatment of Malignant Melanoma cancerous cells, as a
natural product, Sulforaphane has other added advantages in the body of the victims as outlined
below
 Sulforaphane helps in the balancing of the body hormones
 Sulforaphane helps people in losing weight
 Sulforaphane helps in protection of liver
 Sulforaphane helps improve kidney health
 Sulforaphane cures diabetes
 Sulforaphane supports mitochondria functionalities
Efficacy of Temozolomide in Treatment of Malignant Melanoma
When malignant melanoma is diagnosed at its early stages, primary surgical treatment
has proved to cure the victims. However, under deeply invasive cases of melanoma, there is a
high possibility of evolving distant metastases. Initially, Adjuvant therapy had proved to be
partially effective but the current systemic treatment has borne disappointing results. The
disappointment has opened a chance for temozolomide tests which indicated a promising future
for malignant melanoma (Garbe et al, 2016, p.201). Temozolomide works in the same
mechanism just as the dacarbazine; unlike in the case of dacarbazine, however, temozolomide
has proved to have oral bioavailability and has the ability to cross the blood-brain barrier. These
additional benefits of temozolomide indicate its efficacy in treating patients with frequent
metastatic melanoma.
Temozolomide mechanism of action

ASSESSING THERAPEUTIC EFFICACY IN THE TREATMENT OF MALIGNANT MELANOMA 5
The therapeutic advantages of temozolomide mainly depend on its capability to
methylate the victim’s DNA, which mainly occurs at N-7 and/ or O-6 positions of the guanine
residues. Methylation interferes with the DNA and leads to the death of tumor cells. Some tumor
cells can, however, repair this kind of DNA damages.
Efficacy of Vemurafenib in Treatment of Malignant Melanoma
Compared to chemotherapy, vemurafenib has shown its efficiency in the treatment of
BRAF-mutated metastatic melanoma according to the approval done by FDA and EMA. A study
carried out to determine the efficacy and safety factor of vemurafenib therapy for metastatic
melanoma indicated an improved survival rate in patients who had BRAF V600 mutation (Hua et
al, 2016, p.50).
Efficacy of Dabrafenib in Treatment of Malignant Melanoma
Introduction of MEK and BRAF inhibitors into medical practice has enhanced in the
diagnosis of patients of metastatic melanoma. However, the additional element, dabrafenib into
these two inhibitors has indicated its superiority in administering single agent therapy
characterized by tolerable spectrums of adversative events which implies a decline in incidences
over treatment time (Hua et al, 2016, p.46).
The main aim of this paper is to scrutinize and analyze the efficiency of the four medical
approaches: Sulforaphane, Temozolomide, Vemurafenib, and Dabrafenib in the treatment of
Human Malignant Melanoma (A375) and Normal Keratinocyte (HaCat) Cell Lines
(Gospodarowicz, Brierley and Wittekind, 2017). The main objectives of the paper are therefore
to exposure the cancerous cells associated with these two diseases to compounds with different
concentrations in order to determine the effective concentration which can cure the diseases ,

ASSESSING THERAPEUTIC EFFICACY IN THE TREATMENT OF MALIGNANT MELANOMA 6
investigate therapeutic effectiveness of different combinations of curative compounds of
malignant melanoma cells(A375) as assessed under the keratinocytes cells (HaCat) to assess the
safety level when using those compound , determine the effectiveness of the natural product
Sulforaphane as compared to the chemical drugs like Temozolomide, Vemurafenib And
Dabrafenib in the fight against Malignant Melanoma cancerous cells. Lastly, cell viability will be
evaluated using spectrophotometric techniques (Chinembiri et al, 2014, p.11700).
The first hypothesis of the study is to come up with a therapeutic approach which is
unique from other research studies and that utilizes compounds in human malignant melanoma.
Keratinocytes (HaCat) cells will then be used to test therapeutic approach chosen to ensure the
safety of the skin. The second hypothesis is to come up with a combinational therapeutic
approach that is based on the actions of different drugs used in clinical practices and which are
completely experimental like natural products.
References
Chinembiri, T.N., Du Plessis, L.H., Gerber, M., Hamman, J.H. and Du Plessis, J., 2014. Review
of natural compounds for potential skin cancer treatment. Molecules, 19(8), pp.11679-11721.
Dreyer, F., Cantone, M., Eberhardt, M., Schuler, G., and Vera, J., 2016. 501 A web-based
comprehensive map including regulatory pathways subverted in melanoma that can be

ASSESSING THERAPEUTIC EFFICACY IN THE TREATMENT OF MALIGNANT MELANOMA 7
visualized, browsed and used for analyzing cell line and patient high throughput data. Journal of
Investigative Dermatology, 136(9), p.S246.
Esteva, A., Kuprel, B., Novoa, R.A., Ko, J., Sweater, S.M., Blau, H.M. and Thrun, S., 2017.
Dermatologist-level classification of skin cancer with deep neural networks. Nature, 542(7639),
p.115.
Gospodarowicz, M.K., Brierley, J.D. and Wittekind, C. eds., 2017. TNM classification of
malignant tumors. John Wiley & Sons.
Garbe, C., Peris, K., Hauschild, A., Saiag, P., Middleton, M., Bastholt, L., Grob, J.J., Malvehy,
J., Newton-Bishop, J., Stratigos, A.J. and Pehamberger, H., 2016. Diagnosis and treatment of
melanoma. European consensus-based interdisciplinary guideline–Update 2016. European
Journal of Cancer, 63, pp.201-217.
Hua, C., Boussemart, L., Mateus, C., Routier, E., Boutros, C., Cazenave, H., Violet, R., Thomas,
M., Roy, S., Benannoune, N. and Tomasic, G., 2016. Association of vitiligo with tumor response
in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatology, 152(1),
pp.45-51.
Pilgrim, W., Hayes, R., Hanson, D.W., Zhang, B., Boudreau, B., and Leonfellner, S., 2014. Skin
cancer (basal cell carcinoma, squamous cell carcinoma, and malignant melanoma): new cases,
treatment practice, and health care costs in New Brunswick, Canada, 2002–2010. Journal of
cutaneous medicine and surgery, 18(5), pp.320-331.
Svedman, F.C., Pillas, D., Taylor, A., Kaur, M., Linder, R. and Hansson, J., 2016. Stage-specific
survival and recurrence in patients with cutaneous malignant melanoma in Europe–a systematic
review of the literature. Clinical epidemiology, 8, p.109.

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