Background: The phophatidylinositol 3-kinase (PI3K) pathway is critical in regulating diverse
cellular functions and its deregulation is associated to one third of human cancers. Therefore, several
PI3K inhibitors have been developed with many of these entering preclinical and early clinical assessments.
Structure based design has led to the development of broad array of agents including dual
inhibitors of PI3K and mTOR, pan-PI3K inhibitors and isoform specific inhibitors for cancer therapy.
However, as we move towards deeper clinical assessment, there are challenges with regards to therapeutic
index, toxicity profile, overcoming feedback loops and the like. This review explores these classes of
PI3K inhibitors, their strategies and progress in clinical assessment.
Method: A structured search of bibliographic databases was undertaken for peer-reviewed literature
using a focused review query. The quality of retrieved articles was assessed using standard tools. The
contents of the screened articles were ananlyzed to deduce interventions and findings extracting the
quintessence in a conceptual framework.
Results: A total of 104 papers have been referenced in the review that includes research papers, review
articles, conferences/meetings proceedings and theses. The papers were studied and assessed according
to our objective and classified for the refinement of the data to be extracted from them. This review
identifies classes of PI3K inhibitors and the status of these inhibitors in terms of its clinical value.
Conclusion: This review precisely talks about the finding and strategies of PI3K inhibitors in clinical
development. Though the future of PI3K inhibitors against cancer might seem beaming, there are challenges
to face regarding strategic development, clinical regimen, tolerability and limited monotherapy