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Skin Cancer: Genetics, Immunology, Treatments, and Psychological Care

Abstract

Non-melanoma skin cancer (NMSC), consisting of basal cell carcinoma and squamous cell carcinoma , is considered the most common form of malignancy in humans. Melanoma is another major skin cancer, accounting for a small percentage of skin cancers, but is the deadliest form of skin cancer. Several players contribute in the pathogenesis of skin cancers, including genetics and epigenetics, various types of immune cells, and environmental risk factors. During recent years, some novel genes, numerous new therapeutic options, and also some new approved drugs associated with skin cancer have been introduced in the literature. Moreover, psychological care, which might be underestimated and remains unmet in case of many patients, is being emphasized of late. Considering the fact that skin cancer is a multifactorial condition that could be developed or influenced by genetic alterations, immune system alterations, and also environmental and lifestyle changes, it needs to be discussed from different points of view. In this chapter, all the mentioned factors were discussed both in case of NMSC and melanoma. After giving a clinical insight, risk factors, clinical manifestations, and the pathology of these conditions, recognized mutated genes as well as rare syndromes associated with NMSCs and melanoma have been discussed. Additionally, epigenetic factors (methylation, histone modifications, and microRNAs) have also been introduced. Since immune responses are the determinants of outcome, the role of the most studied immune cells in skin cancer patients such as T cells, natural killer cells, dendritic cells, macrophages, and mast cells have been discussed in detail. There is also some limited evidence of the contribution of autoimmune diseases and some viruses in the pathogenesis of skin cancer. Having an overview of the signaling pathways involved in skin cancer development and several clinical trials has led to the approval of some drugs belonging to various treatment strategies, including targeted therapy , immunotherapy , and the oncolytic viruses. These treatments seem to be potent enough to replace traditional non-surgical treatment options for skin cancer. Since patients with cancer not only need physical improvement but also psychological Interventions, the last section of this chapter covers the psychological issues in patients with skin cancer. Psychological outcomes, psychoneuroimmunology, and supportive cares for those who suffer from psychological problems are covered in this chapter.

Keywords

  • Non-melanoma skin cancer
  • Basal cell carcinoma
  • Squamous cell carcinoma
  • Melanoma
  • Psychology
  • Target therapy
  • Immunotherapy

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Abbreviations

5-FU:

5-fluorouracil

AA:

Alopecia areata

ACT:

Adoptive cell transfer

AK:

Actinic keratosis

ALA:

Δ-5-aminolevulinic acid

ALM:

Acral lentiginous melanoma

APCs:

Antigen-presenting cells

BCC:

Basal cell carcinoma

BCNS:

Basal cell nevus syndrome

CM:

Cutaneous melanoma

CMV:

Cytomegalovirus

COX:

Cyclooxygenase

CTLA-4:

T-lymphocyte-associated protein 4

DCs:

Dendritic cells

DDEB:

Dominant dystrophic epidermolysis bullosa

DEB:

Dystrophic epidermolysis bullosa

EB:

Epidermolysis bullosa

EBV:

Epstein–Barr virus

EGFR:

Epidermal growth factor receptor

EV:

Epidermodysplasia verruciformis

FAMMM:

Familial atypical multiple mole-melanoma

FAMMM-PC:

Familial atypical multiple mole-melanoma-Pancreatic Cancer

FDA:

U.S. Food and Drug Administration

FSD:

Ferguson-Smith disease

GG-NER:

Global genome nucleotide excision repair

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HBV:

Hepatitis B virus

Hh:

Hedgehog

HHV8:

Human Herpesvirus 8

HLA:

Human leukocyte antigen

HPA:

Hypothalamic–pituitary–adrenal axis

HPV:

Human papillomavirus

HSV:

Herpes simplex virus

HWs:

Hispanic whites

IDO:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon-gamma

IL:

Interleukin

iNKT cells:

Natural killer T cells

JEB:

Junctional epidermolysis bullosa

KIR:

Killer cell immunoglobulin-like receptor

KS:

Kaposi Sarcoma

LAG-3:

Lymphocyte-activation gene 3

LMM:

Lentigo maligna melanoma

MAL:

Methyl ester

MAS:

Melanoma-Astrocytoma syndrome

MBAITs:

BAP1-mutated intradermal tumors

MCC:

Merkel Cell Carcinoma

MCs:

Mast cells

MIS:

Melanoma in situ

miRNA:

MicroRNA

MM:

Malignant melanoma

MSSE:

Multiple self-healing squamous epithelioma

NBCCs:

Nevoid basal cell carcinoma syndrome

NF-κB:

Nuclear factor-kappa-B

NGF:

Nerve growth factor

NHWs:

Non-Hispanic whites

NK cell:

Natural killer cell

NKT cell:

Natural killer T cell

NMSCs:

Non-melanoma skin cancers

non-HS RDEB:

Autosomal recessive dystrophic epidermolysis bullosa, Non-Hallopeau-Siemens type

NSAIDs:

Non-steroidal anti-inflammatory drugs

OCA:

Oculocutaneous albinism

OTRs:

Organ transplant recipients

PD-1:

Programmed death 1

PDT:

Photodynamic therapy

PFS:

Progression-free survival

PGE2:

Prostaglandin E2

PUVA:

Psoralen and ultraviolet A radiation

RA:

Rheumatoid arthritis

RDEB-HS:

Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type

RT:

Radiation therapy

SA:

Sympathetic axis

SCC:

Squamous cell carcinoma

SLE:

Systemic lupus erythematosus

SLNB:

Sentinel lymph node biopsy

SNPs:

Single-nucleotide polymorphisms

SP:

Sub-stance P

SSM:

Superficial spreading melanoma

T4N5:

T4 endonuclease V

TAMs:

Tumor-associated macrophages

Tc:

Cytotoxic T-cell

TGF-β:

Transforming growth factor-beta

Th:

T helper

TILs:

Tumor-infiltrating lymphocytes

TIM-3:

T-cell immunoglobulin and mucin-domain containing-3

TNF-α:

Tumor necrosis factor-alpha

T-VEC:

Talimogene laherparepvec

UV:

Ultraviolet

UVR:

Ultraviolet radiation

VDR:

Vitamin D receptor

VEGF:

Vascular endothelial growth factor

XP:

Xeroderma pigmentosum

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Tavakolpour, S., Daneshpazhooh, M., Mahmoudi, H. (2017). Skin Cancer: Genetics, Immunology, Treatments, and Psychological Care. In: Mehdipour, P. (eds) Cancer Genetics and Psychotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-64550-6_18

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