PIK3CA gene aberrancy and role in targeted therapy of solid malignancies.
Owen WillisKhalil ChoucairAbdurahman AlloghbiLaura StanberyRex MowatF Charles BrunicardiLance DworkinJohn NemunaitisPublished in: Cancer gene therapy (2020)
Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various signaling pathways that drive oncogenesis. Hyperactivation of the PI3K/AKT/mTOR pathways-either via mutations or genomic amplification-confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Contradictory reports exist in the literature regarding the prognostic value of PIK3CA in aggressive cancers, but most available data highlights an important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways have been investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of the PI3K/AKT/mTOR pathway in cancer and examines association with the clinico-pathological parameters and prognosis.
Keyphrases
- poor prognosis
- copy number
- protein kinase
- long non coding rna
- systematic review
- signaling pathway
- genome wide
- randomized controlled trial
- emergency department
- big data
- cell proliferation
- transcription factor
- artificial intelligence
- genome wide identification
- endoplasmic reticulum stress
- deep learning
- squamous cell
- induced apoptosis