Table 3:

Emerging clinical opportunities for PI3K inhibitors

Therapeutic strategy	Therapeutic area	Disease indication	Expected effect of drug
PI3Kα inhibitors	Cancer	Solid tumours, most effective in PIK3CA-mutant cancers? (key indications in breast cancer, head and neck cancer and ovarian cancer)s	Direct anti-proliferative effects on cancer cells
			Potentiation of hormone therapy (breast cancer)
			Overcoming anti-HER2 resistance (breast cancer)
			Sensitization to PARP inhibitors or paclitaxel (ovarian and breast cancer)
			Anti-angiogenesis?
			immunomodulation?
	Non-cancer	PROS	Reduction of tissue overgrowth
			Anti-seizure effects
		Obesity and metabolic syndrome	Decrease in adiposity
PI3Kδ inhibitors	Cancer	B-cell malignancies	Direct anti-tumour effects (anti-proliferative / non-cytotoxic)
			Interference with B-cell/stroma interaction
		Solid tumours (most effective in ‘immune hot’ tumours)	Activation of host anti-tumour immune response
			Direct anti-tumour effects in PI3Kδ-expressing cancers?
	Non-cancer	APDS	Normalisation of deregulated immune signalling as consequence of PI3K activation
		Auto-immunity/inflammation?	Normalisation of overactive immune signalling
		Diabetic retinopathy?	Dampening of angiogenesis and immunomodulation in endothelial cells
		Infectious diseases such as Leishmania	Enhanced innate myeloid cell responses
			Dampened regulatory T and B lymphocyte responses
Pan-PI3K inhibitors	Cancer	B-cell malignancies	Direct anti-tumour effects (non-cytotoxic)
			Interference with B-cell/stroma interactions
			Activation of a host anti-tumour immune response?
		Solid tumours	Direct anti-tumour effects
			Interference with how tumour cells modulate their stroma?