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Page 83
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY
www.irjponline.com ISSN 2230 – 8407
Review Article
A REVIEW ON SKIN CANCER
S. Ramya Silpa1*, Chidvila V2
1M. Pharmacy, Pharmacology, Sai Coral County, Aravinda nagar, Anantapur, India
2M.pharmacy, Pharmacology, Assistant professor, St. Marys College of Pharmacy, St. Francis Street, Secunderabad, India
*Corresponding Author Email: shilpasankarapu@gmail.com
Article Received on: 19/07/13 Revised on: 20/07/13 Approved for publication: 12/08/13
DOI: 10.7897/2230-8407.04814
IRJP is an official publication of Moksha Publishing House. Website: www.mokshaph.com
© All rights reserved.
ABSTRACT
Skin cancer can be of 2 t ypes mainly. They are malignant melanoma a nd non-malignant melanoma. Skin cancer mainly occurs due to exposure of sunlight.
Ozone depletion and chemical exposures are other factors involved in precipitating skin cancer. Mutations of p53 gene are involved in UV- induced
carcinogenesis. P53 gene acts vital in development of SCC. So, prevention of skin cancer is the main criteria. Regular application of sunscreens could be one
of the primary preventi on. The purpose of present review is to outli ne types, pathogenesis, diagnosis, prevention and treatment of skin cancer.
Keywords: Skin cancer, BCC, SCC, melanoma, UV-light.
INTRODUCTION
Skin
The skin is an organ that separates human body and
environment. It acts as a barrier that protects body against
UV-radiation, toxic substances, infections.1 Epidermis is the
outermost layer of skin. Keratinocytes, dendritic
melanocytes, Merkel and Langerhans cells are different type
of cells present in epidermis. The underlying dermis contains
connective tissue with antigen presenting dermal dendritic
cells, mast cells and memory T-cells.2,3
Skin Cancer
The incidence of skin cancer in people has been increasing
day by day. The main reason for skin cancer is due to UV-
exposure because large amounts of UV-radiation reach
earth’s surface due to depletion of ozone layer.4,5 Skin cancer
can be of two types mainly. 1. Malignant melanoma 2. Non
malignant melanoma; which is divided into BCC and SCC;
BCC and SCC mainly occur due to chronic exposure of UV-
sunlight. MM may be due to intense sun exposure and history
of sun burn.6,7 80-85 % of non-melanoma skin cancers are
BCC and SCC. SCC is more dangerous and is responsible for
many deaths. Skin cancer in early stage can be cured easily
by simple procedures or techniques but advanced skin cancer
cannot be treated effectively by any medications. So there is a
need to detect and treat disease at early stage.8 Over all, 80 %
of skin cancers are BCC, 16 % are SCC and 4 % are
melanoma.9
Figure 1: Skin Cancer
Etiology
The causes for NMSC are environmental and host factors.
Environmental factors associated with NMSC are sun
exposure, ozone depletion, and chemical exposures. Host
factors are HPV, genetic susceptibilities, skin tone and
immunosuppression.10-12 Outdoor workers are more prone to
skin cancer as they may easily get affected by UV-exposure.
Exposure during weekends and holidays are involved in
chronic exposure to UV-light in children.13,14
Prevalence
Generally fair skin, red and blond hair, blue or green eyes are
more susceptible to skin cancer.15-18
Signs and Symptoms of Melanoma
· Changes in size, shape or color of mole19.
· Oozing or bleeding from mole.
· A mole that feels itchy, hard, lumpy or swollen.
Types of Skin Cancer
Basal cell carcinoma (BCC)
Figure 2: Basal Cell Carcinoma
The most common type of skin cancer is basal cell
carcinoma. They generally occur in head and neck regions
followed by trunk and extremities. They usually arise from
basal layer of epidermis.7,20 BCC is again classified into 3
types; Superficial, nodular and sclerosing / morpheaform.
Superficial form of BCC can be seen in trunk and extremities
as an erythematous plague. Nodular BCC lesions generally
seen on the head and neck and appear as pearly, telangiectatic
S. Ramya Silpa et al. Int. Res. J. Pharm. 2013, 4 (8)
Page 84
papules with rolled borders. Morpheaform lesions often
resemble scars and usually are the most difficult to identify
on visual inspection alone, often lacking the pearly and
telangiectatic characteristics seen in superficial and nodular
BCCs. Gorlin syndrome patients are often associated with
BCC. These people usually have BCC at centre of face or at
any anatomical site.21 NMSC like BCC and SCC arise from
keratinocytes. BCC undergo metastasis rarely but it has
tendency to cause more morbidity. But SCC undergoes rapid
metastasis. They may occur due to chronic sun exposure and
can be seen on different parts of sun-exposed areas of the
body.22,23
Epithelial Skin Cancer and Oncogenic Virus Infection
Non melanoma skin cancers like BCC, SCC, AK are most
commonly occurring types in transplanted patients. AK is
found to be precursor for BCC and SCC. AK was found to
occur 15 years prior in transplanted patients compared to
normal people. AK is found to be more frequent in heart than
in kidney and liver transplants. SCC > BCC can be seen in
transplanted patients and it is vice-versa in general
population.24-28
Kaposi Sarcoma
This is more commonly seen in elderly people. This occurs
mainly due to virus named KS associated human herpes virus
(KSHV) called as HHV-8.29-33 Lower limbs; trunk and at last
upper limbs are the targeted regions for Kaposi sarcoma to
occur. It can also involve oral mucosa, lymph nodes, stomach
and duodenum.34
Neuroendocrine Skin Cancer (Merkel cell carcinoma)
It usually occurs at head, neck and extremities of elderly
people. Immunosuppression plays an important role in
formation of such type of skin cancer. MCC in transplanted
patients found to be elevated when compared to normal
people.35
Melanoma
Figure 3: Melanoma
Melanoma is less common than other skin cancers. However,
it is much more dangerous if it is not found early. It causes
the majority (75 %) of deaths related to skin cancer.36 This
type of skin cancer is associated with melanocytes of
epidermal layer. They synthesize melanin pigment that
produces cells of skin with photo protection from mutagenic
UV-rays. MM is less common compared to BCC and SCC.
The treatment for melanoma completely is not familiar. There
is less curable rate for melanoma. Prevention is best method
for melanoma.37-39. It is the only preventable cancer that
continues to increase.40
Squamous Cell Carcinoma
SCC is considered to be second most common type of cancer
in US with 250000 cases diagnosed annually. It is usually
seen in black and Asian Indians representing 30 % to 65 % of
skin cancers in both races. It occurs on sun exposed sites of
head and neck. Generally, the long-term outcome is positive,
as less than 4 % of Squamous-cell carcinoma cases are at risk
of metastasis (and hence life-threatening)39,41
Figure 4: Squamous Cell Carcinoma
Pathophysiology
UV-light is a major cause for skin cancer. Both UV-A and
UV-B play a crucial role in causing skin cancer.42
UV-induced DNA Damage
Sunlight can be categorized into three types depending on
wavelength UVC (200 – 280 nm), UVB (280 – 320 nm) and
UVA (320 -400 nm). UVC do not reach earth surface as it is
filtered by ozone layer. UVB (1 – 10 %) and UVA (90 – 99
%) reaches earth surface.5 UVB is primarily responsible for
DNA damage. It has the tendency to induce all phases of skin
cancer. (Initiation, promotion and progression).43 As the
ozone layer is slowly depleted due to environmental changes,
large amount of UV-light reaches earth surface. This is
responsible for increased incidence of skin cancer all over the
world. Research implies that there is positive correlation
between skin cancer and past UV exposure.44 Sun beds are
also involved in etiology of skin cancer. UVA has constituted
much higher proportion of total UV released by these devices
relative to that in solar radiation since early 1980’s.45
UVB-induced MAPK Signaling Pathways. UVB has been
shown to signal through the MAPK cascade and includes
ERK, JNK and p38. In this simplified model, UVB-
irradiation activates acidic sphingomyelinases which in turn
activates ceramide followed by activation of atypical PKCs.
Atypical PKCs (PKC-_ or PKC-_/_) phosphorylate and
activate MEK, followed by ERK. ERK phosphorylates and
activates TCF which then binds with SRF to an SRE site
within the promoter of specific genes. Activation of this
pathway results in c-Fos expression followed by AP-1
activation. UVB also activates PKC_ and _ followed by
activation of JNK and c-Jun. Another affect of UVB is
activation of the p38 pathway. UVB can also induce
signaling through the Ras pathway. The ultimate result of
these signal transduction cascades is a cellular response such
as proliferation, differentiation, apoptosis or tumorigenesis.
The postulated molecular targets of the chemoprevention
agents EGCG, perillyl alcohol, aspirin, and retinoids are
shown.5 If a foreign antigen enters into human body, immune
system gets activated and fights against foreign antigen. But
incase of UV-radiation, this phenomenon doesn’t occur
because UV can cause the suppression of immune system that
t leads to inadequate prevention of tumor development.46
S. Ramya Silpa et al. Int. Res. J. Pharm. 2013, 4 (8)
Page 85
Figure 5: UVB-induced M APK Signaling Pat hways
This is most commonly seen in elderly people; because they
have weak immune system power. Immunosuppressive drugs
like cyclosporine, steroids and azathioprine can potentially
impair SIS defence capacity leading to an increased incidence
of different types of skin cancer.47-50
Mutations of p53 Gene in Skin Cancer
P53 is crucial in maintaining genomic integrity by blocking
DNA replication in response to DNA damage from exposure
to agents like UV-light.51,52 Exposure to normal epidermal
keratinocytes to UV-light results in transient increase in p53
protein levels and resultant arrest in G1 phase of cell cycle.
So, mutations of p53 can be seen in UV- induced
carcinogenesis. P53 gene plays a predominant role in
development of SCC.5,53-56
Prevention
At most, there is a need to educate the people about skin
cancer completely. So, that there might be a chance to
prevent skin cancer to some extent. The measures to be taken
to prevent skin cancer include staying out of the sun during
hottest part of the day, wearing or applying sunscreen when
expose to sunlight, avoiding exposure to sunlamps. Use of
sun beds need to be prevented.19 SEB: It is biological event
that takes place between exposure and subsequent
development of cancer. They acts as predictors to identify
persons that are on verge of developing cancer. BCC or SCC
incidence and multiplicity, AK incidence and multiplicity are
considered to be clinical or histological endpoints that are
targets for human skin cancer chemoprevention trials.
Wearing protective clothes found to be best method to
prevent skin cancer during sun exposure. Even though
effective sunscreen lotions prevent direct exposure to sun and
UV-light, they have the capacity to prevent formation of
BCC and SCC and mixed. Some trials indicates no effect on
NMSC incidence can be seen by using sunscreens.57,58
Primary prevention involves regular application of
sunscreens along with protective measures recommended by
the World Health Organization (WHO), the International
Commission on Non-Ionizing Radiation Protection (ICNIRP)
and the European Society of Skin Cancer Prevention
(EUROSKIN). Secondary prevention involves early
assessment of malignancies that are curable in early stages of
development; because skin cancer can’t be treated completely
at later or advanced stage. So, there is a need for secondary
prevention.14
Treatment
The first step in the evaluation of skin cancer in patients
comprises of thorough history, focusing on general medical
and drug history, personal and family history of skin cancer,
number of moles including presence of dysplastic naevil and
comprehensive social history, carcinogen or sun
exposure.59,60 The choice of treatment should be determined
by the histological type of the lesion, its size and location,
and the age of the patient. No single treatment method is
ideal for all lesions.61 The treatment goals are total removal
of the tumor, preservation of function, and a good cosmetic
outcome. Curettage and electro desiccation, cryosurgery,
topical chemotherapy, laser surgery, radiotherapy,
immunotherapy, Mohs micrographic surgery, and
conventional surgical excision are all effective therapeutic
options for selective types of BCC.42,62 As the treatment for
skin cancer needs to be initiated at early stage, intervention
soon after diagnosis is required for effective cure of disease.
Radiotherapy is effective in treating early stage lesions.63
New molecular therapeutic approaches for skin cancer
include several medications like cryosurgery,
immunomodulation with imiquimod, 5-FU, photodynamic
therapy and radiation. Small molecule regulators have been
identified for variety of pathways that leads to skin cancer.
The pathways are SHH, Ras / Raf, P17INK4A/CDK4/Rb and
ARF / p53. Research mainly focuses on these pathways and
treatment for skin cancer can be augmented by small changes
of pathways.64-66
Chemotherapy for Melanoma Skin Cancer
Several chemo drugs may be used to treat melanoma:
Dacarbazine (also called DTIC), Temozolomide, Paclitaxel,
Carmustine (also known as BCNU), Cisplatin, Carboplatin,
Vinblastine, Dacarbazine, temozolomide and paclitaxel may
be given either alone or along with some of the other drugs
on the list. It is not clear if using combinations of drugs is
more helpful than using a single drug, but it can add to the
side effects like hair loss, mouth sores, loss of appetite,
nausea and vomiting, diarrhea, increased risk of infection
(from too few white blood cells), easy bruising or bleeding
S. Ramya Silpa et al. Int. Res. J. Pharm. 2013, 4 (8)
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(from too few blood platelets), fatigue (from too few red
blood cells).67
Treatment for BCC
Primary radiotherapy is considered to be treatment of BCC
involving nose, lower eyelids or ears. The limitation for
radiotherapy is lack of histological control of margins and
fault that often leads to inadequate or excessive treatment.
Morpheaform of BCC found to be resistant to radiotherapy
treatment. Morpheaform, mutatypical, adenoid,
basosquamous and infiltrative types can be treated with
Mohns surgery or conventional surgical excision.62 So, the
early detection of skin cancer is the key to cure especially in
malignant melanoma. Several sensitive mole imaging
systems are available in market that has the tendency to
identify lesions that might ordinarily missed using standard
clinical tools.68
How to Examine
There should be a method to the examination that allows for
visual scanning of the entire surface of the patient’s skin
before focusing on individual suspect lesions. The feet and
hands including the palms, nails and areas between the toes
and fingers should be examined. The anterior of the body
then the posterior surface should be examined, including the
intertriginous areas. If the patient gives consent, the border
zones of the oral and ocular mucosae and genital area should
also be examined. Special attention should be paid to the
head and neck region, and the scalp should also be examined
with a combination of direct visual examination and
palpation. Dermascopic examination of individual lesions can
allow visualization of deeper layers of the skin and, in expert
hands, can be useful. However, practitioners must be trained
in its use and the significance of dermascopic changes. In the
most common skin cancers, the genetic traits of an individual
form the base upon which environmental factors established
over a period interplay to result in disease. Pale complexion,
light-coloured eyes, red or blond hair (related to
nonfunctioning MC1R mutations2),69 freckles and a Northern
European or Celtic background are important risk factors.
Squamous cell carcinoma (SCC) is more common in outdoor
workers and occurs on body sites of maximum sun exposure.
The ears and lower lips are frequently unprotected and may
be exposed to cocarcinogens, e.g. tobacco. SCC at these sites
is more aggressive, with a significantly higher risk of
metastases.70
CONCLUSION
The incidence of skin cancer has been drastically elevating
day-to-day. Skin cancer in early stage can be cured easily by
simple procedures or techniques but advanced skin cancer
cannot be treated effectively by any medications. So there is a
need to detect and treat disease at early stage. Overall, 80 %
of skin cancers are BCC, 16 % are SCC and 4 % are
melanoma. UV-A and B are mainly responsible for skin
cancer. Outdoor workers are more prone to skin cancer
because they get easily exposed to skin cancers. So,
precautionary measures like application of sunscreen lotions
need to be done. SEB play an important role in identifying
extent of skin cancer in particular person. It can be treated at
initial stages, as the duration is extended, the chances for
treating skin cancer gets hastened. New molecular therapeutic
approaches for skin cancer include several medications like
cryosurgery, immunomodulation with imiquimod, 5-FU,
photodynamic therapy and radiation.
Abbreviations
AK: Actinic keratosis
BCC: Basal Cell carcinoma
ERK: Extracell ular Signal-Regulated Kinases
EUROSKIN: European Society of Skin Cancer Prevention
HHV-8: Human Herpes Virus-8
ICNIRP: Ionizing Radi ation Protection
KSHV: Kaposi's sarcoma-a ssociated herpes virus
MM: Malignant M elanoma
MAPK: Mitogen acti vated Protein Kinase
NMSC: Non melanoma skin cancer
PKC: Protein Kinase C
SCC: Squamous cell carcinoma
SEB: surrogate Endpoint Biomarker
WHO: World Health Organization
UV: ultra violet
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Cite this article as:
S. Ramya Silpa, Chidvila V. A review on skin cancer. Int. Res. J. Pharm.
2013; 4(8):83-88 http://dx.doi.org/10.7897/2230-8407.04814
Source of support: Nil, Conflict of interest: None Declared
