Chapter 6 **Squamous Cell Carcinoma: Biomarkers and Potential Therapeutic Targets 135**

Vlad-Mihai Voiculescu, Constantin Caruntu, Iulia Solomon, Mihai Lupu, Mihaela Adriana Ilie, Daniel Boda, Carolina Constantin and Monica Neagu

Preface

skin cancer at least once.

The annual incidence of all forms of human skin cancer are increasing, representing a grow‐ ing public concern. Human skin cancers are by far the most common type of tumors and so represent a significant health burden to the society: it is estimated that the annual cost is \$8.1 billion for all skin cancers combined, of which some \$3.3 billion is devoted to melanoma1

Nearly 5 million people are treated in the United States each year for various skin cancers,

the elderly and it has been estimated that half of all Americans who live to age 65 develop

The deadliest skin cancer is unquestionably melanoma. If detected early it is curable by re‐

Stage 0: Melanoma in situ, the cancer is only in the epidermis. Stage 1: Up to 2 millimeters (mm) deep, not spread to lymph nodes or other sites. Stage 2: Melanoma thicker than 1 mm, may be thicker than 4 mm, not spread to lymph nodes or other sites, may or may not be ulcerated. Stage 3: Spread to local lymph nodes or nearby lymphatics, but not spread to dis‐ tant sites. The primary cancer may be thicker than 4 mm, and it may be ulcerated. Stage 4: Metastatic melanoma has reached distant lymph nodes or metastasized to additional organs;

It is estimated that 50% of all melanomas have an activating mutation in the *BRAF* gene,

to specifically target mutated BRAF proteins. Two such drugs, vemurafenib and dabrafe‐ nib, have been approved by FDA for the treatment of late-stage melanomas. MEK is a BRAF effector protein, it acts downstream from BRAF, and therefore is another attractive target for melanoma therapy. Drugs that block MEK proteins, trametinib (Mekinist) and cobimetinib (Cotellic),have been shown to shrink some melanomas with mutated BRAF changes. Gener‐ ally, they are used in combination therapy, with BRAF inhibitors, because they are expected

A very promising new approach for melanoma treatment is immunotherapy, an approach that boosts patient's own immune system to identify and defeat cancer cells more effective‐ ly. These drugs work by eliminating the restraints from the body's immune system. Pembro‐ lizumab (Keytruda) and nivolumab (Opdivo) inhibit PD-1, a protein that prevents immune

against melanoma cells, leading to diminished tumors and prolonged lives. These drugs of‐ ten cause serious side effects. Ipilimumab (Yervoy) also boosts the immune response, but it

Alternatively, interferon-alfa and interleukin-2 are proteins that boost the immune system in

. They were shown to shrink advanced melanomas in about 10% to 20% of

most commonly liver, lungs, bones and brain are affected by these metastases.

to delay the development of resistance to BRAF-targeting monotherapies5

targets a different protein, CTLA-4, another immunity check point7

with melanoma, the deadliest, killing nearly 9,000 people yearly2

section, however at later stages it is often deadly3

which promotes unrestrained melanocyte proliferation4

cells from attacking other cells in the body6

patients and may be given together.

a general way8

.

. Skin cancer is a disease of

. Melanoma stages 0 – 4 are described as:

. Novel drugs have been developed

.

. Blocking PD-1boosts the immune response

.

Chapter 7 **Correlation between Porcine and Human Skin Models by Optical Methods 161**

Alessandra Keiko Lima Fujita, Rozana Wendler da Rocha, André Escobar, Andrigo Barboza de Nardi, Vanderlei Salvador Bagnato and Priscila Fernanda Campos de Menezes

Chapter 8 **Molecular Mechanisms and Biomarkers of Skin Photocarcinogenesis 175** Adriana T. Lopez, Liang Liu and Larisa Geskin
