Biology of Cancer ✅ Flashcards
What is cancer?
Uncontrolled cellular proliferation
What prevents excessive replication of normal cells?
Most healthy cells have limited potential for replication and their proliferation, differentiation, and death is carefully controlled
What happens to cell division during cancer development?
Cells undergo a multi-step process in which they gradually acquire genetic mutations allowing them to escape the normal controls
What can cancers be divided into?
- Benign, or low-grade
- Malignant, or high-grade
What are the features of low grade tumours?
- Tends to grow locally
- Has not developed the potential to metastasise
What are the features of high grade tumours?
- Highly proliferative
- Tends to metastasise
How is it determined if a tumour is ‘highly proliferative’?
Has high mitotic index when examined under the microscope
When might a benign tumour not have a benign clinical course?
If the tumour is growing close to and impinging on a vital structure
What must happen for a cell to become malignant?
Mechanisms designed to prevent cancer development must be overcome
What are the key processes by which a cell becomes malignant?
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signs
- Immune escape
- Limitless replicative potential
- Tumour-promoting inflammation
- Tissue invasion and metastasis
- Inducing angiogenesis
- Genetic instability
- Evading apoptosis
- Abnormal cellular metabolism
What do normal cells require to trigger them to proliferate?
External signals (growth factors)
How can cells develop self-sufficiency in growth signals to become cancerous?
- Mutations in cell surface receptors so that they are constitutionally active even in the absence of growth factors
- Expression of abnormally high levels of cell surface receptors
What do normal cells have to prevent excess proliferation?
Multiple anti-proliferative signals
Give an example of an anti-proliferative signal
Contact with neighbouring cells
What is the purpose of anti-proliferative signals?
Maintain tissue stability and prevent overgrowth
How can cells change to overcome anti-proliferative signals to become cancerous?
They can acquire mutations such that they become insensitive to these signals
What is meant by a limited replicative potential of cells?
Normal cells are able to divide a limited number of times before they enter a state known as senescence
What controls the limited replicative potential of cells?
Successive shortening of telomeres
What are telomeres?
Repetitive sequences of DNA base pairs that cap the end of chromosomes
What happens to telomeres following each replication?
Some of their base pairs are lost
How can cells acquire limitless replicative potential to become cancerous?
They can develop the ability to overcome telomere shortening
How can cells develop the ability to overcome telomere shortening?
By re-expressing telomerase that allows them to rebuild lost telomeres, or through other mechanisms
What is apoptosis?
Inbuilt mechanisms to trigger programmed cell death
Why might a cell trigger apoptosis?
In response to significant DNA damage or other insult
How can cells evade apoptosis to become cancerous?
The balance between pro and anti-apoptotic signals is altered
What does a cancer cell need to do to in order to metastasise?
Acquire a number of abilities, including;
- The ability to invade into blood vessels or lymphatic system
- The ability to survive as a single detached cell or clump of cells
- The ability to invade the target tissue and survive in this new environment
Why is it important for cancer cells to be able to induce angiogenesis?
As tumours grow, they need to ensure the development of new blood vessels to ensure adequate supply of oxygen and nutrients
How do cancer cells induce angiogenesis?
They produce various signals, such as vascular endothelial growth factor (VEGF), that stimulate the growth of new blood vessels
What is meant by immune escape in cancer cells?
The development of mechanisms by which they can evade detection and elimination by the immune system
Why is it important that cancer cells develop the ability to evade the immune system?
There is growing evidence for a role of the immune system in controlling cancer development
What is the importance of non-cancer cells within a tumour?
They may play a role in stimulating tumour growth
Give an example of when a non-cancer cell within a tumour may play a role in stimulating tumour growth
Inflammatory cells enhancing angiogenesis
Why is genetic instability important in the development of cancerous cells?
Cancer cells need to acquire multiple genetic mutations in order to achieve many of the characteristics required to survive, and increased genetic instability helps enhance the acquisition of these mutations
Why is abnormal cellular metabolism important in the development of cancerous cells?
Cancer cells must survive in relatively inhospitable tissue environments, and so many cancer cells alter their energy metabolism as an adapation
Give an example of when a tumour may have an inhospitable tissue environment
Marked hypoxia at the centre of a large tumour
What can genetic abnormalities in cancer be divided into?
- Those that result in the over-activation of a particular gene or pathway
- Those that result in a loss of function
Give 2 examples of where gain of function mutations can lead to enhanced malignant progression
- Growth factor receptor signally pathways
- Transcription factors
By what mechanisms can a gain of function mutation occur in a proto-oncogene?
- Translocation
- Amplification
- Point mutations
How might translocation of a proto-oncogene lead to a gain of function mutation?
Can lead to increased expression of the oncogene driven by the promoter region of another gene, or the formation of a novel fusion protein with abnormal activity
How can amplification of a proto-oncogene lead to cancer?
It leads to increased oncogene expression
What can point mutations in proto-oncogenes be divided into?
- In promoters (at the beginning of a gene)
- Within a gene
How can a promoter point mutation in a proto-oncogene lead to cancer?
Leads to increased oncogene expression
How can a point mutation within a proto-oncogene lead to cancer?
It may lead to expression of a protein with abnormal activity
In what kind of genes can a loss of function mutation lead to cancer?
Tumour suppressor genes
Give 2 examples of functions of tumour suppressor genes
- Trigger apoptosis
- Block cell cycle progression in the presence of DNA damage
