Skin Cancer Flashcards by Jamie Barclay

What are the three types of skin cancer?

Melanoma
Squamous cell carcinoma
Basal cell carcinoma

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What are the keratinocyte skin cancers?

Squamous cell carcinoma

Basal cell carcinoma

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where are keratinocytes?

in the epidermis

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What layer of the epidermis does basal cell carcinoma arise?

the basal layer

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What layer of the epidermis does squamous cell carcinoma arise?

the suprabasal layer

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Where does melanoma arise from?

Melanocytes

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Where are melanocytes?

Scattered along the basal layer

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What percentage of cancers are non-melanoma skin cancers?

1/3

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of non-melanoma skin cancers, how many are basal cell carcinomas?

3/4

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of non-melanoma skin cancers, how many are squamous cell carcinomas?

1/4

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What is the difference between basal cell carcinomas and squamous cell carcinomas?

Basal cell carcinomas cannot metastasis

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What is squamous cell carcinoma associated with? Therefore who does it effect the most?

Cumulative UV-exposure

Elderly people

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Who are at higher risk of developing squamous cell carcinoma?

Those who are immunosuppressed

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What percentage of squamous cell carcinomas are linked to immunosuppression?

11%

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What percentage of metastatic squamous cell carcinomas are linked to immunosuppression?

40%

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What is the issue with UVA?

It is very prevalent
Longer wavelength and therefore penetrates deeper in the skin
Causes indirect DNA damage

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What is the issue with UVB?

It causes direct DNA damage

1,000 times more damaging than UVA

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How does UVB induce DNA damage?

It is incorportated into the DNA helix -> forms covalent linkages to form cycloburane pyramidine dimers (CPDs) and 6,4 photoproducts -> interferes with base pairs during DNA replication -> mutation

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Which photoproduct is more common, CPD or 6,4 photoproduct?

CPDs

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Which photoproduct is more mutagenc, CPD or 6,4 photoproduct?

6,4 photoproducts

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What are sun sensitive people?

Burn easily

Tan poorly

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What increased your risk of skin cancer?

Being sun sensitive 
Sun exposure 
Genetic 
Immunological factors 
Environmental carcinogens 
Age 
Photosensitising drugs 
Human papillomavirus

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How can sun exposure increase your chance of developing skin cancer?

Dose and pattern
The latitude
If you burnt in childhood
Intensive intermittent exposure

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How can genetics increase your chance of developing skin cancer?

Skin type
Albinism
Xeroderma pigmentosum

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How can immunological factors increase your chance of developing skin cancer?

Immunosuppression Malignancies HIV

What environmental carcinogens increase your chance of developing skin cancer?

Ionising radiation Arsenic Trauma

What is xeroderma pigmentosum?

When you cannot repair the damage

why do sun sensitive people burn and not tan?

they produce pheomelanin instead of eumelanin | Pheomelanin absorbs UV less effectively

What do freckles mean?

You cannot tan

What is solar lentigines?

Sun induced permanent freckles

What do sunburn and solar lentigines mean?

UVB damage

What is solar ageing?

Skin ageing

What is solar ageing associated with?

penetration by UVA effecting elastin fibres and collagen

What is sunburn caused by?

a protective measure where keratinocytes are badly UV-damaged and undergo apoptosis

How much does childhood sunburn increase your chances of melanoma?

4 fold

How is chronic UV exposure immunosuppressive?

Dendritic cells lose abilities to present antigens T cells switch from helper to suppressor (Tregs dominate) Keratinocytes and dendritic cells secrete immunosuppressive cytokines

How does immunosuppression increase cancer risk?

Remove immune surveillance

In transplant patients, how much is SCC risk increased?

100-200 fold

In transplant patients, how much is BCC and melanoma risk increased?

5-10 fold

How are bone marrow transplant patients effected in terms of SCC?

It is more aggressive, more metastatic and do not tend to respond to treatment

What pathway tends to be effected in BCC?

Hedgehog signalling, involving PTCH

How many people tend to develop inactivating mutations in PTCH?

90%

Apart from PTCH, what other mutation occurs in BCC and how often does this occur?

Activating mutation in SMO | 10%

What drug inhibits the hedgehog pathway?

Vismodegib

What is the side effects of Vismodegib?

Effects the dermal capillaries on the tongue and effects peoples taste buds and makes them unable to eat

What percentage of melanomas have a Braf mutation?

50%

What is the critical transcription factor in melanoma?

MITF

What does vemurafenib target?

BRAF V600E

Name a anti-CTLA-4 drug

Ipilimumab

Name a anti-PD-1 drug

Pembrolizumab

Why is anti-PD-1 typically used by itself?

Patients cannot tolerate the dose in combination

What did whole genome sequencing of SCC show?

They have large number of copy number changes

What is a sign of SCC development?

Actinic keratoses

What is chronic sun exposure associated with?

Increase clone size

What is the issue with p53 mutations and continued sun exposure in SCC?

If you have a p53 mutation in the beginning then you will not get apoptosis, however, further skin exposure can cause the p53 mutations to expand without the need for other mutation

what gene is most highly mutated in cSCC?

NOTCH

How many cSCCs have NOTCH1 and/or NOTCH2 mutations?

82%

What is NOTCH?

A tumour suppressor and oncogene depending on the conext

What cancers is NOTCH an oncogene in?

T-acute lymphoblastic leukaemia Chronic lymphoblastic leukaemia B-cell malignancies

What cancers is NOTCH a tumour suppressor in?

Head and neck SCC

What is FAT1?

A negative regulator of Wnt/beta-catenin

What is signature 32 associated with?

Immunosuppression

What increases signature 32?

Azathioprine (immunosuppressive drug)

How does azathioprine induce cancer?

It is metabolised -> incorporated into DNA -> produces ROS when exposed to UVA -> damages DNA -> decreased nucleotide excision repair -> increase mutagenesis

What is DNA 6-TG?

a UVA photosensitiser

If a patient has to receive azathioprine, what should they also do?

Photoprotect

What is the primary prevention against skin cancer?

Photoprotection | Diet and drug

What is the secondary prevention against skin cancer?

Surgery if it might be invasive SCC Lesion directed destructive treatments Topical agents e.g. 5-FU and Imiquimod Photodynamic therapy

Give an example of a lesion directed destructive treatment

Cryotherapy

What is the issue with photodynamic therapy?

It is typically not well tolerated

What does Imiqumod do?

Increases the immune system to remove the tumour

What are retinoids used for?

helps to differentiate the skin and prevents early lesions from developing?

Why do retinoids have to be used at low doses?

If you take a patient off them, e.g. due to side effects, the lesions rebound so better to use at low doses for life than higher doses and rebound occur

Skin Cancer Flashcards

(73 cards)