3323 [Hallmarks Of Cancer]

Front 1

What are 10 hallmarks of cancer? Which ones are the emerging hallmarks and enabling characteristics?

Back 1

Evading apoptosis; Self-sufficiency in growth signals; Insensitivity to Anti-growth signals; Tissue invasion and Metastastis; Limitless replicative potential; Sustained Angiogenesis;

EH: Deregulating Cellular Energetics, Avoiding Immune Destruction

EC: Genome Instability and Mutation, Tumour promoting inflammation

Front 2

How do cancer cells evade apoptosis?

Back 2

Through mutating apoptotic sensors like cell surface receptors that bind death factors or intracellular sensors that monitor DNA damage. They can also mutate apoptotic effectors like caspases, which break down cell organelles

Front 3

How do cancer cells obtain self sufficiency in growth signals?

Back 3

Normal cells require external growth signals to move from a quiescent state to a proliferative state. Tumour cells generate their own growth signals through mutating downstream signalling molecules or overexpressing the receptors in permanently activated forms

Front 4

How do cancer cells become insensitive to anti-growth signals? Provide an example

Back 4

Through ignoring signals that encourage differentiation and responding exclusively to those that keeps them in a quiescent state. eg Myc-Max factor maintains pluripotency and Mad-Max encourages differentiation. Cancers ignore Mad signalling, reactivating Myc - making more Myc-Max

Front 5

The pRB/E2F pathway is key to directing the G1 to S transition [enables replication]. What is the function of anti-growth signal TGFbeta in this pathway? How does cancer manipulate it?

Back 5

TGFbeta blocks the phosphorylation of pRB, preventing the E2F from being an active transcription factor. Cancers however mutate this pathway, increasing E2F and cell division

Front 6

Why do cancer cells require sustained angiogenesis?

Back 6

Cells in tissue need to be ~100um from a blood vessel otherwise they’ll die from hypoxia and nutrient starvation. Hence, as tumours grow, new blood vessels need to be formed otherwise this expansion will not be sustainable

Front 7

How do cancer cells have limitless replicative potential?

Back 7

Cells eventually senesce after a limited number of divisions due to shortening of telomere length. Hence tumours maintain telomere length to allow for more divisions through:

- upregulating telomerase production (80-90% of cancers) and

- Alternative Telomere Lengthening (ALT) mechanism that uses homologous recombination and extension (10-20%)

Front 8

How do cancers invade tissues and metastasise?

Back 8

Tumours change the integrins they produce, degrading focal adhesions and adheren junctions. This results in EMT, whereby cells exhibit biased migration to disorganised matrices rather than to matrices of epithelial phenotype

Front 9

What are the enabling characteristics of cancer and what do they do?

Back 9

1. Genome Instability: Cancer cells increase sensitivity to mutagenic agents and decrease efficiency of DNA repair

2. Tumour promoting Inflammation: Tumours are infiltrated by immune cells carrying out inflammation and they hijack this process in order to acquire additional growth factors, survival factors, proangiogenic factors, ECM modifying enzymes, and release ROS that help mutate nearby cells.

Front 10

What are the emerging hallmarks of cancer? (Not widely accepted, still contentious)

Back 10

1. Deregulating Cellular Energetics: Described by the Warburg Effect - Whereby even in aerobic conditions, cancer cells tend to produce energy via glycolysis rather than the more efficient oxidative phosphorylation pathway which is the preference of most other cells in the body

2. Avoiding the Immune System: Cancer cells avoid the constant surveillance of the immune system. Paradox: Highly immunocompromised people do not have a higher burden of non-virally triggered cancer

Front 11

Hallmarks can be considered the defining features that make cancer cells different to normal cells. Yet, do you need all hallmarks to contract cancer? What do the enabling characteristics do?

Back 11

Yes.

Help the tumour acquire the hallmarks

Front 12

What are the limitations of the hallmarks model?

Back 12

1. Model suggests each hallmark is considered equal but some cancers rely more heavily on others

2. Metastasis is the real issue in cancer, as the first 5 hallmarks are common to both benign and metastatic tumours. Further understanding of this process is what’s needed.

Front 13

Death signals converge on mitochondria to cause release of ___.

An ___ is a gene that has the potential to cause cancer

Tumour cells generate their own growth signals eg. ___ made by glioblastoma or ___ by sarcoma

Back 13

cytochrome C

oncogene

Platelet derived growth factor; tumour growth factor alpha

Front 14

Angiogenesis is an ___ step required for formation of macroscopic tumours

___ requires changes to the physical coupling of tumour cells to the stroma and activation of extracellular proteases

Back 14

early-to midstage

Tissue invasion and metastasis

Front 15

Note any other mechanisms by which cancer cells produce more vasculature aside from sprouting angiogenesis

Back 15

Recruitment of endothelial progenitor cells; Vasculogenic mimicry (tumour cells line up and form BVs); Intussusceptive angiogenesis (BVs in BVs); Use of lymphatic cells to form BVs; Vessel cooption (using normal cell BVs for themselves)