**Possibilities for the Therapy of Melanoma: Current Knowledge and Future Directions Knowledge and Future Directions**

**Possibilities for the Therapy of Melanoma: Current** 

DOI: 10.5772/intechopen.70368

Marcela Valko-Rokytovská, Jana Šimková, Mária Milkovičová and Zuzana Kostecká Mária Milkovičová and Zuzana Kostecká Additional information is available at the end of the chapter

Marcela Valko-Rokytovská, Jana Šimková,

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.70368

#### **Abstract**

This chapter presents an overview of possibilities for the therapy of melanoma, current knowledge and future direction. Skin cancer is one of the most frequent types of cancers. Melanoma is much less common than basal cell and squamous cell skin cancers, but it is far more dangerous. Detailed knowledge of melanoma at the molecular level allows to develop new treatment alternatives and to design effective new drugs. There are two approaches in therapy of melanoma in the present based on immunotherapy and targeted therapy or their combination. Immunotherapy includes immune checkpoint blockades, whereas targeted therapy is represented by protein kinase inhibitors, such as BRAF inhibitors, MEK inhibitors, and NRAS inhibitors. Detailed knowledge of protein structure and the understanding of its role in key signaling pathways in melanoma development lead to the designation of new protein kinase inhibitors in targeted therapy.

**Keywords:** melanoma, chemotherapy, immunotherapy, targeted therapy, protein kinase inhibitors

#### **1. Introduction**

The incidence of melanoma is increasing worldwide. Melanomas represent 3% of all skin cancers but 65% of skin cancer deaths [1]. Melanoma is currently the fifth and sixth most common solid malignancy diagnosed in men and women, respectively [2]. The rates of melanoma have been rising for at least 30 years [3]. Although melanoma is no longer considered just 'one disease', pathologists will continue to have important role in identifying and describing tumor subtypes [4]. More detailed understanding of melanoma allows the development

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

of new specific treatment alternatives, which are targeted at specific receptors or the genes of tumor cells. In 2011, new molecules were discovered and designed on the basis of new knowledge in the molecular biology of melanoma. These new facts have resulted in the existence of two new approaches to therapy: immunotherapy and targeted therapy of melanoma.

The incidence of melanoma is increasing at one of the highest rates of any form of cancer in fair-skinned populations around the world. The exposure to sunlight during the past 50 years is an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show stabilization in Australia, in North America, and also in European countries. Prevention campaigns aim on reducing incidence and achieving earlier diagnosis, which resulted in an ongoing trend toward thin melanoma since the last two decades. However, the impact of primary prevention measures on incidence rates of melanoma is unlikely to be seen in the near future; rather, increasing incidence rates to 40–50/100,000 inhabitants/year should be expected

Possibilities for the Therapy of Melanoma: Current Knowledge and Future Directions

http://dx.doi.org/10.5772/intechopen.70368

111

The possible signs and symptoms of melanoma are new moles or spots on the surface of skin that are changing in size, shape and color. Another important sign is a spot that looks different from all of the other spots on skin. There are the **ABCDE** criteria for these signs, which

**C** – Color; the color is not the same all over and may include shades of brown or black, or

**D** – Diameter; the spot is larger than 6 mm across, although melanomas can sometimes be

The classification schemes **Breslow's thickness (depth)** and **Clark's level** have been developed based on either the vertical thickness of the lesion in millimeters or the anatomic level of invasion of the layers of skin. Breslow's depth is considered significant factor in predicting the progression of the melanoma. Increased tumor thickness is correlated with metastasis and poorer prognosis. Tumors are classified into four categories based on the depth: thickness of 0.75 mm or less, thickness of 0.76–1.5 mm, thickness of 1.51–4 mm and thickness greater than

Clark's level of invasion has far less importance and is used only in the staging of thin mela-

Level II – melanoma invades papillary dermis but not papillary-reticular dermal interface;

in Europe in the next decades [15].

guide to the usual signs of melanoma:

smaller than this.

4 mm.

**3. The possible signs and symptoms of melanoma**

**B** – Border; the edges are irregular, jagged, or blurred.

sometimes with patches of pink, red, white, or blue.

**4. Melanoma classification and staging**

nomas (<1 mm). Tumors are classified into five levels:

Level I – melanoma involves only epidermis (melanoma *in situ*);

**E** – Evolving; the nevi are changing in size, shape, or color.

**A** – Asymmetry; one half of a nevi or birthmark does not match the other.
