Cancer Flashcards
Cancer
group of diseases generally characterised by genomic instability + uncontrolled cell division and leading to invasion of surrounding tissue and eventual dispersal to distant sites
- positive feedback cycle
- heterogenous and diverse types
Metastasis
Tumor growth in other parts of the body (often deadly)
- break through basal lamina (difficult)
- invades capillaries
- adhere to blood vessel wall in another tissue
- extravasation (escapes from blood vessel)
- proliferate to form metastasis (difficult)
Angiogenesis
Cancer cells direct and promote formation of how blood vessels to themselves. Without this, tumor size is limited to a few mm cubed this allows tumor bulk and growth. Provides means of escape around body as well.
Tumor Types
- malignant - can metastasise, often lethal
- benign - self limiting so are small and don’t metastasise
- carcinoma = epithelial cells
- lymphoma = lymphocyte
- leukemia = white blood cells
- sarcoma = bone/connective tissues
Causes of Cancer
- inherited
- genetic mutations
- viral
Genetic Mutation and Cancer
- point mutations (eg. misregulation of deamination process turning C to U)
- deletions
- translocations
- inversions
Aneuploidy
Presence of abnormal number of chromosomes in a cell - affects a large number of genes and proteins
Inherited Cancer
eg. breast cancer can be caused by precursor mutations BRCA1 and BRCA2 that are involved in gene stability so mutations here lead to subsequent cancer promotion
Clonal Origin of Cancer
Theory that all cancer cells originate from single ‘founder’ cell that developed the mutation that allowed it to become cancerous
However, subsequent cells develop mutations that cause distinct subpopulations to form within the tumor
Darwinian selection leads to further mutations and selection of cancer cells that can survive best in response to selection pressures
Chronic Myelogenous Leukemia
- Caused by a chromosomal translocation (Philadelphia chromosome) that leads to a mutant and hyperactive protein kinase ABL-BCL
- treated by engineering molecular ‘off’ switches, but drug treatment also provides a selection pressure
Colon Cancer
Colon Cells are exposed to a harsh environment that promotes cell turnover so increases risk of mutation developing
Key Mutations : loss of Apc (G1 cyclin regulation), activation of K Ras, loss of p53 (loss of apoptosis)
Tumor Suppressor Genes
- promote proliferation
- dominant action
- acceleration
- mutant gene constituitively active
- must lose both copies for carcinogenesis
Oncogenes
- retard proliferation
- recessive action
- brakes
- normal gene = normal function
2 Hertiable properties of cancer
- reproduction in defiance of normal cell growth restraints
2. invasion and colonization of territories reserved for other cells
Altered Growth Control of Cancer Cells
- divide in suspension
- divide when touching other cells
- continue moving and dividing in confluence
- Warbug effect (metabolic alteration)
- survive stress/DNA damage > apoptotic misregulation
- avoid senesence
- metastasize
- genetically unstable
