What is cancer? Flashcards
Define cancer.
The uncontrolled growth of abnormal cells that is both invasive and metastasising to secondary sites.
In what type of tissue do the majority of cancers arise?
Epithelial tissue
What is an adenoma?
A benign tumour of the glandular structures in epithelial tissue
What is a carcinoma?
Cancer of epithelial cells
What is an adenocarcinoma?
A malignant tumour of the glandular structures in epithelial tissue
What types of cancers are classified by their effect on haematopoietic and immune cells?
Leukaemia (arise in BM - abnormal WBC)
Lymphoid
Myeloid (Affects all myeloid cells - WBC, platelets, RBC..)
Which cells commonly give rise to brain tumours?
Glial cells or neuroblast (embryonic cell)
What is the difference between a mutation in germline cells and somatic cells?
Germline mutations PREDISPOSE
Somatic mutations CAUSE
How does one mutation result in the development of a many cells with the mutation?
The mutated cell will undergo MONOCLONAL growth
Why does cancer not appear to be monoclonal in the late stages?
The cells become heterogeneous as more mutations accumulate and develop.
The genes that mutate in cancer usually have a function in control. What functions will this affect?
Growth, Cell cycle, Receptors, Stemness (ability to self renew and differentiate into different types of cells), apoptosis, integrity and repair of DNA
Why may a mutation occur?
Due to copying errors in DNA replication.
Exposure - UV, radiation
Spontaneous depurination (chemical damage)
What must the mutation provide in order to develop into a malignancy?
Must provide a growth advantage to the cell, allowing it to survive and invade
What are the two main types of genes commonly affected in cancer?
TSG
Oncogenes
What is the function of a TSG? How is the function lost in cancer?
Negatively regulates growth. Must lose BOTH alleles to lose the suppressor effect.
What is an oncogene? How is the function lost in cancer?
Positive regulator of growth. Overexpression and activation may occur with the mutation of only ONE allele.
What are the 6 hallmarks of cancer?
The characteristics of a tumour cell that allows it to be malignant and metastasise.
- Self sufficiency in growth signals
- Intensity to anti-growth signals
- Evasion of apoptosis
- Limitless replication potential
- Sustained angiogenesis
- Tissue invasion and metastasis
Describe the self sufficiency in growth signals hallmark.
A mutation in a receptor causes continuous signalling through ligand-independent firing, despite the lack of an extracellular signal.
The receptor may also produce its own GF in response to an autocrine signal.
Describe the intensity to anti-growth signals hallmark.
Disrupting the TSG pathway of pRB results in loss of control over G1 to S phase progression. Loss of pRB leads to over proliferation.
Describe the evasion of apoptosis hallmark.
p53 is pro-apoptotic. It decides if cell damage can be reversed. If a cell is stressed, p53 levels increase for repair or death. If it is lost or mutated, DNA repair will be disrupted and the cell will evade apoptosis.
The cancer will either increase anti-apoptotic and decrease pro-apoptotic.
Describe the limitless replication potential hallmark.
When a cell divides its telomere shortens, limiting the number of times it can divide. Once it reaches its limit it will become senescent.
Cancer cells express telomerase so they can proliferate without telomeres.
What is the purpose of a telomere?
To limit the number of divisions and to prevent fusion with neighbouring chromosomes.
Decribe the sustained angiogenesis halmark.
Tumours are highly metabolic, requiring high blood supply for oxygen and nutrients. Mutations will allow control of transcription of pro-angiogenic inducers and downregulate inhibitors for the sprouting of vessels.
Hypoxia plays a role in this.
Describe the tissue invasion and metastasis hallmark.
Epithelial tumours can change there morphology to a mesenchymal cell for migration and metastasis. The cells change the adhesion molecules, cadherins and integrins.
Secondary site preparation occurs through the secretion of cytokines to attract cells and form a microenvironment.
Metastatic spread is determined by the genes of the primary tumour as to where they travel to.
What are the two emerging hallmarks?
Deregulating cellular energetics - changes in cellular metabolism and stroma
Avoiding immune destruction
What are the two enabling characteristics?
Mutations in genes, maintaining stability and DNA repair give advantage to tumour cells.
Tumour promoting inflammation - Immune cells provide factors to support the tumour, by suppressing the immune system.
