Hypoxia and its impact on the tumour microenvironment of gastroesophageal cancers

Table 1 Hypoxia induces the transcription of a range of genes that mediate diverse roles in promoting the hallmarks of cancer[178-180]

Function	Gene
Enzymes	MMP1, MMP3, LOX, ADAMST1, ACE
Transcription factors	Twist1, Snail, Slug, β-Catenin, c-Myc, Oct4, NF-κB
Receptors	CXCR4, c-Met, TLR4, Notch
Growth factors	VEGF, TGFα
Transporters	Glut-1, MDR1
Intracellular signalling	Cdc42, Rac1, RhoE
Bioenergetics	LDHA, PGK1, PKM2, GAPDH, GPI, ALDOC

Table 2 Techniques used in the measurement of tissue oxygenation and their associated advantages and disadvantages[10,181-183]

Technique	Advantages	Disadvantages
Needle Electrodes	Instrumental in establishing the link between hypoxia and treatment failure	Prone to sampling error due to poor spatial resolution
	Real time direct measurement	Invasive and requires direct access to tumours
Exogenous Markers	More sensitive than electrodes at lower oxygen levels	Requires biopsy and immunohistochemistry
	Reproducible
	Precise spatial resolution
Endogenous Markers	Precise spatial resolution	Requires biopsy and immunohistochemistry
	Can be serological such as Osteopontin
	Can be tissue based such as HIFs or carbonic anhydrase IX
Radiological	Non-invasive	Expensive
	Reproducible	Radiation exposure
	Precise spatial resolution	Relatively less well established

HIF: Hypoxia inducible factor.