Targeting cancer with PI3K pathway inhibitors: who to aim at?

Breast and gynecological (ovarian, endometrial and cervical) cancers commonly harbor mutations activating the PI3K pathway, including PIK3CA mutation/amplification, PTEN loss or HER2 amplification. Insight from the successful development of many targeted cancer therapeutics suggests that these tumor types with a high prevalence of mutations in the PI3K pathway would be ideal candidates for therapy with inhibitors of that pathway. This was indeed the case with imatinib to target Bcr-Abl positive CML patients and cKIT mutant GIST tumors; vemurafenib to target B-RAF^V600E melanoma; trastuzumab to target HER2 positive breast cancer; and crizotinib to target EML4-ALK positive lung tumors.