Lecture 1A: Nature of Cancer Flashcards
What are the key keywords in cancer description?
- malignant - divides out of control
- mutations - cancer develops from a single cell that has undergone a number of mutations
- apoptosis - fail to undergo programmed cell death
- invasion and metastasis - some of the cells develop abnormal capacity to invade normal tissue and metastasize
What are the hallmarks of cancer?
- sustaining proliferative signalling
- evading growth suppressors
- activating invasion and metastasis
- enabling replicative immortality
- inducing angiogenesis
- resisting cell death
- deregulating cellular energetics
- avoiding immune destruction
- tumor-promoting inflammation
- genome instability and mutation
- unlocking phenotypic plasticity
- nonmutational epigenetic reprogramming
- polymorphic microbiomes
- senescent cells
Where do majority of human cancers arise from?
from epithelial tissues
What are carcinomas?
malignant epithelial cells penetrate the basal membrane of the epithelium and invade adjacent tissue
Where do sarcomas arise from?
From connective tissue
What is the mechanism of cancer spread?
1) Local invasion (e.g. breast cancer, brain primaries)
2) Haematogenous spread (e.g. colon cancer spreads via portal vein to the liver)
3) Lymphatic spread (e.g. breast cancer to axillary lymph nodes)
4) Transcoelomic spread (e.g. ovarian cancer spreading throughout peritoneum)
Why is cancer so serious? How does it cause its effects?
- Accumulation of tumour mass in vital organs interrupts essential normal bodily functions (e.g. respiration, liver function, renal excretion, brain function, bone marrow)
- Large tumour mass places a metabolic demand on the body
- Tumours may secrete factors that have an adverse effect on the body
- TNF [tumour necrosis factor] causes cell death in adjacent normal tissue to facilitate tumour growth
- PTHrP [parathyroid hormone-related protein, responsible for bone resorption and humoral hypercalcaemia] stimulates the expression of genes involved in heat production in adipose tissues and has an important role in tissue wasting)
Why does cancer cause death?
- can be directly related to tumour (major airway obstruction, liver failure)
- can be secondary to general debility caused by the cancer (pneumonia)
- sometimes - unknown
How do cancers arise?
- most are from genetic alterations
i) mostly found in the DNA of somatic cells
ii) results in defects in cellular control genes
iii) these may be precipitated by environmental mutagens (cigarette smoke, UV irradiation) - only about 5-10% cancer is hereditary
What are the steps of colorectal tumourigenesis?
- loss of APC turns normal epithelium to hyper-proliferative epithelium
- Activation of K-ras turns early adenoma into intermediate adenoma
- loss of SMAD4 turns intermediate adenoma to late adenoma
- loss of p53 turns late adenoma into carcinoma
- where then various genetic alterations cause carcinoma to metastasize
What is APC?
adenomatous polyposis coli - tumour suppressor in Wnt signalling pathway
What is K-ras?
oncogene - activation of MAPK signalling pathway
What is SMAD4?
tumour suppressor in TGF-β signalling pathway
What are oncogenes?
- accelerate cell divison
- cancer arises when stuck in ‘on’ mode
What are tumour suppresor genes?
- the cell’s brakes for tumor growth
- cancer arises when the brakes fail
