Mechanisms of oncogenesis Flashcards
List the risks/prevention of cancer
Alcohol/smoking Physical activity Diet/obesity Inherited genes Air pollution/radon Infections and HPV UV Hormones
What is cancer
Group of diseases characterised by:
Abnormal cell proliferation
Tumour formation
Invasion of neighbouring normal tissue
Metastasis to form new tumours at distant sites
What are carcinomas
Epithelial cells ~85%
Cancer that develop from epithelial cells
What are sarcomas
Cancer derived from mesoderm cells
What are adenocarcinomas
Cancers in glandular tissue
10 hallmarks of cancer
Evading growth suppressors Avoiding immune dysfunction Enabling replicative immortality Tumor promoting inflammation Activating invasion and metastasis Inducing angiogenesis Genome instability & mutation Resisting cell death Deregulating cellular genetics Sustaining proliferative signaling
What do accumulation of mutations over time represent and when do they occur
The multi-step process that underlies carcinogenesis
Occurs after cells defence mech. of DNA repair evaded
What causes cell to escape surveillance
Many mech for carcinogenesis block
But burdening increases possibility of cells escaping
Link between age-cancer
Longer we live the more DNA mutations accumulate = may lead to cancer
What is clonal development
All cells in primary tumour from single cell, intiation of cancer = clonal
What allows for heterogeneity of cells in a tumour
Cells evolve - sub clonal selection = growth advantage
What are tumour cells dependent on
On interaction w/other tumour cells + tumour microenvironment
Explain the importance of control of cell division in self renewing tissues
Important in rapidly self renewing tissues when proliferation must balance cell loss
Carcinogenesis - define
Initiation of cancer formation
Proto-oncogenes - define
Normal genes activated to be oncogenic
Oncogene - define
A mutated proto-O, leading to signals that cause uncontrolled growth
Tumour suppressor genes - functions and describe effect once mutated
Inhibit both growth and tumour formation
Act as braking signals during phase G1 of the cell cycle, to stop or slow the cell cycle before S phase
If tumour-suppressor genes are mutated, the normal brake mechanism will be disabled, resulting in uncontrolled growth, i.e. cancer
Describe 3 assumptions made about carcinogenesis
Malignant transformation of a single cell is sufficient to give rise to a tumour
Any cell in a tissue is as likely to be transformed as same type
Once malignant cell generated = mean time to tumour detection is generally constant
Describe model 1 of carcinogenesis, its:
Focus
Mech
Models
Mutational
Focus = chemical carcinogens
- examples = viruses, tobacco, HPV
Mech = DNA adducts
Models = mutations, oncogenes + armitage-Doll
DNA adducts - define
Covalent modifications of the DNA that result from exposure to specific carcinogens = can serve as biomarker
Describe model 2 of carcinogenesis, its:
Focus
Mech
Models
Genome instability (GI)
Focus = familality + GI
- examples = colon cancer, Rb
Mech = CIN, MIN, MMR, BRCA1, TSG
Model = knudson
Describe model 3 of carcinogenesis, its:
Focus
Mech
Models
Non-genotoxic
Focus = clonal expansion/epigenetics
- examples = diet, hormones
Mech = methylation, histone acetylation
Model = moolgavkar
Describe model 4 of carcinogenesis, its:
Focus
Mech
Models
Darwinian
Focus = clonal expansion/cell selection
Examples = beta-carotene, folate, chemotherapy
Mech = selective advantage
Model = nowak
Describe model 5 of carcinogenesis, its:
Focus
Mech
Models
Tissue organisation
Focus = microenvironment, morphostats
Model = baker
Morphostat
Any biochemical compound responsible for the maintenance of normal tissue microarchitecture
Describe the effect of carcinogens
Alter any of cancers’ processes to induce carcinogenic effects
Can induce DNA damage + act in genotoxic manner
Explain the significance of the presence of multiple mutations in critical genes
Feature of cancer cells + supports that cancer arises through accumulation of irreversible DNA damage
Describe the discovery of specific chemicals that can induce cancer
1915, Katsuburo Yamagiwa = rabbit ears repeatedly treated w/tar = cancer (chemicals = carcinogens)
1940, British chemists - purification of coal tar, proved ability to induce cancer on mice skin
Describe the classes of carcinogens
Chemical = 10 groups = polycyclic aromatic hydrocarbons, aromatic amines,
azo dyes, nitrosamines, carbamates, halogenated compounds,
alkylating agents
Physical = radiation (ionizing/UV) and asbestos
