Intro to Cancer Biology Flashcards
What are the Hallmarks of Cancer?
The list of the distinctive features shared by cancers, as found in Hanahan and Weinberg (2011), describes all the activities cancer cells must be doing in order to survive.
- Sustaining Proliferative Signalling
- Evading Growth Suppressors
- Resisting Cell Death
- Enabling Replicative Immortality
- Deregulating Cellular Energetics
- Promoting Genomic Instability & Mutation
- Tumour Promoting Inflammation
- Avoiding Immune Destruction
- Inducing Angiogenesis
- Invasion and Metastasis
How is the cell cycle normally regulated?
In normal cells, entry into the cell cycle is tightly controlled by a vast array of factors that opposingly inhibit and promote G1 entry. These allow for tight regulation that can respond to a huge variety of stimuli, also producing ‘checkpoints’ or ‘restriction points’ to prevent unnecessary growth.
How is the cell cycle deregulated in cancer cells?
Sustaining Proliferative Signalling & Evading Growth Suppressors
In cancer cells the growth factors (mitogens) are highly stimulated and the division cycle inhibitors are highly repressed. However cancer cells can become so deregulated that they will enter into the cell cycle even without strong activation.
How is apoptosis regulated in normal and cancerous cells?
Under normal circumstances, apoptosis is controlled by the balance of pro-survival and pro-apoptotic signalling factors (extrinsic pathway), as well as happening in response to cellular or genomic damage/stress (intrinsic pathway).
The pro-apoptosis mechanisms are can be attenuated in cancer cells, particularly in tumours that progress to states of high-grade malignancy and therapy resistance.
What occurs during apoptosis?
Apoptosis of a cell is a highly controlled process that involves cell shrinkage and condensation due to breakdown of the cytoskeleton.
Subsequent nuclear collapse leads to membrane blebbing and eventual splitting of the cell into large vesicles called apoptotic bodies that are then phagocytosed by immune cells.
Describe the normal and cancerous regulation of replicative immortality.
Most cell lineages in the body can only divide a limited number of times (around 30-60) before they enter replicative senescence (i.e. irreversible growth arrest). This is accompanied by telomere shortening, which is thought to be responsible for entry into this state as the decay of the telomeres removes their protection of the ends of the chromosomes, leaving them vulnerable to end-to-end fusions.
In a high proportion of cancer cells however, the telomeres are more actively maintained by telomerase, enabling replicative immortality.
Why is angiogenesis a hallmark?
Due to their fast growth, large size and high metabolic rate, tumours require a strong supply of oxygen and nutrients as well as efficient disposal of toxic wastes. To provide this they recruit tumour associated neovasculature through the process of angiogenesis.
What is metastasis?
The most life-threatening part of cancer, this is predicated upon the ability of the tumour cells to break away and travel to a new location to form another tumour, a process that happens in three discrete stages
What are the three stages of metastasis?
• Invasion
This is the process through which the cancer cells are able to dissociate from the primary tumour and move through the surrounding stroma (supportive/connective tissue + vasculature)
• Intravasation
This is the entry of the tumour cell into the bloodstream or lymphatic system through interaction with the epithelium, allowing it to metastasise – be swept away to another part of the body.
• Extravasation
The exit of the tumour cell from the haematogenous or lymphatic systems, allowing it to settle in the parenchyma (i.e. the functional tissue of an organ – non-connective or supportive).
The tumour cell then forms small nodules of cancer cells called micrometastasic lesions that grow into macroscopic tumours.
What are oncogenes?
Oncogenes are genes that, when mutated to produce a gain/increase of function, promote the formation of tumours. Hence the oncogene products – oncoproteins – are responsible for promoting proliferation, growth and survival etc.
What common trait is often shared by oncogenes?
These mutations are typically dominant alleles, as being gain of function mutations the incorrect oncoproteins is inevitably expressed.
What are tumour supressor genes?
Tumour suppressor genes, also called anti-oncogenes, are genes that, when mutated to cause a loss/reduction of function, lead to increased cancerogenesis. Hence they are genes whose products normally supress cancer trends such as proliferation growth and survival.
What common trait is often shared by tumour supressor genes?
These mutations are typically recessive, as if only one allele possesses the mutation the other is likely to be able to compensate.
How often are oncogenic mutations heritable?
Around 90% of cancerogenic mutations (AKA Driver Mutations) are somatic, with only a small proportion being inherited through the germ-line. However, inherited mutations such as the BRCA1 gene can greatly increase the individual’s predisposition towards cancer.
What are cancer genome projects?
Cancer Genome Projects are using high-throughput mutation screening studies to identify sequence variants, somatic mutations and now epigenotypes involved in cancer. In order to be specific to humans this uses human cancer cell lines and, increasingly, human tumour tissue.
