Week 1: Overview of cancer biology/Hallmarks of cancer

Question 1

Hallmark 1: Self-sufficiency in growth signals

Answer 1

• Oncogene is the term given to genes which when mutated or overexpressed, can cause cancer
• Mutations in proto-oncogenes lead to a gain in function
• This leads to constant signalling to promote cell proliferation even with the absence of a growth factor or another signal

Question 2

Hallmark 2: Limitless replicative potential

Answer 2

• Caused by telomere shortening following cell division which limits the number of times a cell divides (Hayflick limit)
• Tumour cells are effectively immortal + can rebuild their telomeres by activating expression of a telomerase
• Not considered a mutation, but rather a change in gene expression

Question 3

Hallmark 3: Insensitivity to anti-growth signals

Answer 3

• Tumour suppressor genes are the opposite of oncogenes, often functioning during DNA damage sensing + repair
• Mutations in tumour suppressor genes leads to loss of function, making it difficult to develop drugs that target them
• In many cases, 2-hits are required to inactivate a tumour suppressor gene simply because there are 2 copies of the genes

Question 4

Hallmark 4: Resistance to apoptosis

Answer 4

• Apoptosis can be triggered in cells by DNA damage + viral infection
• Resistance to apoptosis can therefore develop through the gain + loss of apoptosis-promoting + -inhibiting proteins/factors in mutations + genes expression

Question 5

Hallmark 5: Angiogenesis

Answer 5

• Generation of new blood vessels towards the tumour
• Not commonly seen in many cancers, but often will be quite large when a tumour does have blood vessels
• Not seen in leukaemias or vascular cancers

Question 6

Invasion + metastasis

Answer 6

• 90% of cancer deaths are due to the spread of cancer to distant sites
• Additional cellulars changes are required for the cancer cell to overcome the normal containment mechanisms
• The acquisition of invasive properties is what distinquishes malignant from benign cells
• In many cases, the metastatic tumours are detected first, with the original tumour’s location unknown
• Quite a latee event in the development of cancer + not universally seen
• One of the more complex hallmarks as there are many things happening

Question 7

Hallmark 7: Reprogrammed energetics

Answer 7

• Cancer cells often have altered energetics where metabolism shifts from oxidative phosphorylation to glycolysis
• Since glycolysis is much less efficient at producing ATP cancer cells have to significantly increase glucose uptake through glucose transporters
• We’re not sure why, but we think they do this to allow the increased biosynthesis of key molecules allowing cell proliferation