increase spontaneous DNA mutation rate

decrease DNA methylation

increase oncogene expression

increase telomere length

Increased RNA polymerase activity

Reduced telomerase activity

Increasing E-cadherin-mediated cell-cell contact

Overexpression of growth factor receptors through gene amplification or increased expression

Immune cell infiltration

Recruitment of cancer associated fibroblasts

Migration and invasion

Tumour

growth above 2mm

Transition

Initiation

Promotion

Progression

B cells via immune checkpoint inhibitors that diminish B cell responses

Extracellular matrix via enhanced extracellular matrix synthesis

T cells via immune checkpoint inhibitors that enhance T cell responses

Tumour vasculature via therapies that enhance angiogenesis

Promotion

Initiation

Progression

Transition

Checkpoint receptor interactions between tumour cells and cytotoxic T cells

Checkpoint receptor interactions between tumour cells

Checkpoint receptor interactions between tumour cells and stromal cells

Alkylating chemotherapy

A loss-of-function mutation through point mutations in both alleles

Chromosomal translocation deleting a growth-regulatory gene

 A gain-of-function mutation through a point mutation in one allele

A loss-of-function mutation through a point mutation in one allele

An increase in the number of radial processes emanating from the Bergmann glial cells

A mass migration of granule cell precursors from the external granular layer (EGL) to the internal granular layer (IGL)

An expansion of the granule cell precursors in the external granular layer (EGL)

An increase in the number of Shh-secreting Purkinje cells in the molecular layer

When an individual inherits one dysfunctional allele of a proto-oncogene

When a mutation occurs in the only functional allele of a tumour suppressor gene, rendering it dysfunctional

When a mutation is acquired in a proto-oncogene, rendering it dysfunctional 

When an individual inherits two dysfunctional alleles of a tumour suppressor gene