Cancer lectures Flashcards
What is cancer?
Natural-selection driven process where cells gain fitness advantage relative to counterparts and dominate host tissue
What are metastases?
When mutations result in migration and homing advantage in new location
At how many levels is cancer heterogeneous
1) genetic level: genetically distinct in different locations of tumour and between tumours
2) molecular level : cells regulate differently at transcript levels and in post-translational modification
3) cellular level: Cancer cells capture and restructure tissue hierarchy, more self-renewal than differentiation
4) between tumours, each tumour has distinct characteristics
What is a proto-oncogene?
A gene that could be activated or inactivated by cancer-driven mutations
Draw diagram of what happens to proto-oncogene?
(see notes for diagram)
What are examples of the 3 ways a proto-oncogene can be mutated?
1) point mutation- Epidermal Growth Factor Receptor (EGFR) activated by point-mutation and found in number of cancers
2) Translation- BCR-ABL is a fusion protein made from translocation between chromosomes 9 and 22, found in chronic myeloid leukaemia
3) Gene amplification- MyC is a gene commonly overexpressed in tumours due to enhanced chromatic accessibility of the MyC locus. It is an overall amplifier of gene expression, targeting Cyclin D and E2F
Facilitates progression to S phase and cell proliferation
What happens to genes in tumour supressor category?
Inactivated by mutation, often produce heterozygous recessive allele with no loss of function
Loss of heterozygosity= loss of function ie. need further mutation
What is the exception in this category?
p53, most commonly mutated gene in human cancer, normally at low levels and active as a tetramer
Heterozygous levels don’t maintain normal protein activity
When mutated there is cell cycle progression of cells with defective DNA replication
What happens in the absence of Rb?
Cells more likely to enter cell cycle, divide and gain advantage
What does the modern genome sequencing for cancer diagram look like?
(see notes for diagram)
What are cancer stem cells?
At top of cancer hierachy, sustain tumour growth and development
How can you test for cancer stem cells?
Separate cells on basis of proteins on surface, transplant into animals to see if tumour initiated in mouse
Cancer stem cells= only stem cells with capacity to reconstitute tumour similar to the original one and create more tumours in downstream transplants
Cancer cells can result from…
Mutation in tissue stem cells
Transformations of progenitors normally more restricted in differentiation potential
What makes cancer cells hard to kill?
They can stay quiescent for long periods and only cycle infrequently to make clones that dominate the tumour
Many drugs in clinic preferentially target cycling cells
What are new cancer theraputic strategies?
Need to directly target quiescent cells/ promote cell cycle entry to respond to chemotherapy that kills cycling cells
OR maintain cancer stem cells in permanent quiescent state (like HIV)
