Table 1. A selected list of HSP90 client proteins, mechanism of actions of these proteins and potential target tumours that HSP90 inhibitors could be applied to.

Class of protein	Client protein or interacting protein of HSP90	Mechanism of action	Potential target cancer
Receptor tyrosine kinase	EGFR mutant	Activation of downstream prosurvival pathways, such as PI3K-AKT and MAPK.	NSCLC and glioblastoma
	ErbB2/HER-2		Breast cancer
	KIT		GIST
Signalling molecules or kinases	AKT	Activation of prosurvival proteins and suppression of proapoptotic proteins	Various cancers
	B-Raf mutant	Constitutively activates ERK signalling	Melanoma
	MET	Involved in cellular proliferation, migration, invasion and morphogenesis	Gastric, lung
	CDK4	Phosphorylates and inactivates Rb, allowing cell cycle to proceed	Tumours with CDK4 overexpression
	Death domain kinase RIP	Allows activation of NF-κB and its antiapoptotic signals
Transcriptional factors	HIF-1α	Promoting angiogenesis	Renal cancer
	ERα-receptors	Regulating genes involved in cellular proliferation	Breast cancer
	P53 mutant	Transcription of genes involved in cell cycle arrest or apoptosis	Mutated in ∼50% of cancer
Chimeric fusion-proteins	BCR-ABL	Activates numerous signal transduction pathways in leukaemogenesis	CML
	NPM-ALK	Induces cell transformation and proliferation	Anaplastic lymphoma
Others	Telomerase	Prevents telomere shortening	Various cancers
	Apaf-1	Crucial for apoptosome formation
	Bcl-2	Regulates mitochondrial apoptotic pathway	Follicular lymphoma/small cell lung cancer
	MMP2	Facilitates invasion through cell adhesion, matrix digestion and cell migration	Overexpressed in various cancers

CDK4= cyclin dependent kinase 4; CML=chronic myeloid leukaemia; EGFR=epidermal growth factor receptor; ER=oestrogen receptor; GIST=gastrointestinal stromal tumours; HIF=hypoxia-inducible factor; HSP=heat-shock protein; MAPK= mitogen activated protein kinase; NSCLC= non-small cell lung cancer; Rb=retinoblastoma; RIP=receptor-interactingprotein.