L15: cancer heterogeneity

Question 1

What is the staging of tumours?

Answer 1

o TNM
 T – size/local invasion
 N – spread to lymph nodes
 M – spread to distant sites (metastases)
o Then assigned a staging group
 I-II – localized
 III – nearby invasion
 IV – metastasis

Question 2

What are the two main models of cancer heterogeneity?

Answer 2

Two main models
- Cancer stem cells
o Cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample
- Clonal evolution
o Not mutually exclusive
o May differ between cancer types

Question 3

What is a clonal model of evolution?

Answer 3

Clonal model of evolution
- 1st initiating driver event in the cell (an even that gives a cell a selective advantage in its microenvironment
- When a cell has that advantage it expands, grows
- What can happen during this expansion process is another driver event can happen
- And then you get clonal sweep, newly formed cell B is able to outcompete all the old cells A
- This can happen a number of times

Question 4

How can intratumour heterogeneity be tracked?

Answer 4

tumour cells also die because of hypoxia other things, so they shed DNA into the system, tracking ctDNA

Question 5

How can we overcome intratumour heterogeneity?

Answer 5

Evolutionary therapeutics
- Target clonal events
- Target multiple driver events
- Exploit evolutionary constraints
- Attenuating or exploiting genomic instability – key factor of evolutionary events in cancer
- Competitive release and adaptive therapy

Adaptive therapy
- Evidence for use of pesticides in suppressing pest populations
- Oncologists and patients are pre-occupied by cancer cell death – give maximally tolerated dose continuously until treatment stops working
- Fluctuate the dose to keep the cancer at the same level