Photocarcinogenesis Flashcards
What is carcinogenesis
The process by which a normal cell becomes a malignant cancer cell
What is cancer
An accumulation of abnormal cells that multoply through uncontrolled cell division and spread to other parts of the body by invasion and/ or distant metastasis via the blood and lymphatic system
What are the 3 critical steps of cancer
Normal cells becoming abnormal cells
Abnormal cells growing to form a tumour
Metastasis
What does uncontrolled cell proliferation require
multi step gene damage.
E.g gain of function of oncogenes (accelerator) and loss of function of tumour suppressors (brakes)
What are the 6 hallmarks of cancer
Autonomous growth signals Insensitivity to anti-growth signals Resist cell death (apoptosis) Limitless potential to divide Angiogenesis Invasion and metastasis
What can cause damage to DNA
Carcinogens (smoking, UV light)
Inherited defects
Natural accumulation of DNA damage (increases with age)
What is more harmful to humans UVB or UVA
UVB
How are dimers removed
by nucleotide excision repair
What does an accumulation of photoproducts lead to
Mutation
Genomic instability
Cancer
What can mutations in genes involved in DNA repair lead to
Mutator phenotype whereby cells accumulate further mutations at a greatly increased rate because of failure of DNA repair
What leads to chromosome instability
Damage to genes that control the integrity of cell division
What does UVA cause
Indirect oxidative damage
What does UVB cause
direct DNA damage
What 3 things happen in UV induced immunosuppression
Dendritic cells lose ability to present antigen
T Cells sqitch from helper to suppressor; refulatory T cell predominate
Keratinocytes and DCs secrete immunosuppressive cytokines
What is UVR
a complete carcinogen- mutagenic and immunosuppressive
What are 6 general risk factors for skin cancer
Sunlight (latitidue, sunburn in childhood, intense intermittent exposure) Genetic susceptibility (skin type) Chemicals (drugs, arsenic) Age Immunosuppression HPV
What happens to badly UV damaged keratinocytes due to sunurn
They undergo apoptosis or programmed cell death
What is Naevoid basal cell carcinoma (gorlin’s syndrome)
Autosomal dominant familil cancer syndrome
What is TP53 gene known as
The guardian of the genome
In what conditions is there a TP53 mutation found
AK
Carcinoma in situ
SCC
Collagen 7 deficiency causes what
blistering of the skin from birth
Patients with Collagen 7 deficiency commonly die due to what
metastatic SSC
Give some examples of phototoxic drugs
Voriconazole (antifungal) Thiazide diuretics NSAIDs Anti-TNF Azathioprine
What type of drug may reduce the risk of SCC
mTOR inhibitors
