Chapter 13 - Cancer Heterogeneity

heterogeneity

* diversity, distinguishing characteristics amongst a whole or group
* heterogenous is a similar word

homogeneity

* similarity, consistency
* characteristics that are shared among a whole or group
* homogenous is a similar word

why is cancer not one disease

* cancer is not the same from person to person
* no 2 cases are exactly the same
* there are similar features between cancers (hallmarks)
* there are different features between cancers
* there are also differences between individual tumours or cancer cells coexisting within the same patient

4 sources of cancer heterogeneity

* cancers types arising from different cells, organs, & tissues
* populations vary in their susceptibilities to different cancer types (genetics, environments)
* individuals within a population vary
* evolution of cancer sub clones within an affected individual

heterogeneity in tumour microenvironment

environment within & around the tumour can also be different

basic Darwinian evolutionary principles

* idea of “survival of the fittest”
* natural selection of species in the environment
* some mutations will make new phenotypes
* the ability to survive & reproduce can be affected by these mutations & phenotypes
* mutations that improve survival & reproduction fitness emerge & can eventually lead to new species emerging

cancer and clonal evolution

* mutations in cancer can continue to be acquired over time once the cancer has developed
* often through errors in DNA replication & repair
* this can result in subclones of cancer emerging with acquired differences in genome sequences compared to the parent cline
* mutations can allow advantages that become dominant
* the selective pressure can relate to the ability of various cancer subclones to survive & reproduce in the host

tumours at different anatomical sites ?

may differ from one another

location in the body can ?

drive selective mutations

different organs & tissues require ?

different cancer mutations to survive

2 methods of non-mutational ways of arriving to heterogeneity

* epithelial-mesenchymal transition (EMT)
* cancer stem cell (CSC) hypothesis

epithelial-mesenchymal transition (EMT)

* complex biological process that enables cancer cells to suppress their epithelial features changing to mesenchymal ones
* cells change their behaviour
* change the way the genes are expressed
* EMT is the idea that cells are arising from epithelial cells & can change their behaviour & gene expression
* not actual mutations
* cells are responding to their environment

cancer stem cell (CSC) hypothesis

* hypothesis that cancer cells arise from a cancer stem cell
* a subpopulation of self-renewing cancer cells is capable of replication & differentiation
* results expansion of cancer cell population

EMT & CSC hypothesis both describe ?

phenotypic plasticity

cancer treatment and clonal evolution

the selective pressures on a population of cancer cells can that drive evolution can also come from cancer treatment

what mutations enable cancer cells to survive a given treatment?

a mechanism of acquired/secondary treatment resistance