Title:Triggering PIK3CA Mutations in PI3K/Akt/mTOR Axis: Exploration of Newer Inhibitors and Rational Preventive Strategies
Volume: 22
Issue: 39
Author(s): Vivek Asati, Sanjay K. Bharti, Debarshi Kar Mahapatra, Vikas Asati and Ashok K. Budhwani
Affiliation:
Keywords:
PI3K/PTEN/Akt, PIK3CA, Signaling pathway, Anticancer, Inhibitors.
Abstract: Background: PIK3CA gene was found in generation of p110 alpha (p110α)
protein through an instruction process. p110 alpha acts as a catalytic subunit of
phosphatidylinositol 3-kinase (PI3K) proceed phosphorylation of signal molecules through
PI3K pathway. This PI3K involved in regulation of cellular growth, transformation,
adhesion, apoptosis, survival and motility. In some situations the PI3K/Akt pathway get
altered due to mutation in PIK3CA gene produced oncogenic event in human malignancy.
Methods: The goal of this work is to describe the PI3K signaling pathway including
mutational activation of PIK3CA gene and inhibitors have been developed or under clinical
trials for the targeting of PI3K or PI3KR kinases.
Results: Various inhibitors such as Morpholine, pyrimidines, benzenesulfonamide, pyridopyrimidinone,
imidazo[1,5]naphthyridine, benzeneacylhydrazones, thienopyrimidine,
aminopyridopyrimidine, imidazopyridine, imidazo[1,2-a]pyridine, thiazolopyrimidinone,
quinolines and quinoxalines, thieno[3,2-b]pyran-7-one, morpholino-1,3-benzoxazines, quinalozinones, pyrido
[3,2-d]pyrimidines, benzo[d]thiazol-2-yl)acetamide, aminopyrimidines, chalcone , azaindole, pyrazolopyrimidine
and pyridine, thienobenzoxepin, phenylquinazolines , pyrazolo[1,5-a]pyridines , imidazolo-pyrimidine
etc. were investigated under laboratory level as PI3K inhibitors in which few having PI3K and mTOR dual inhibitory
activities.
Conclusion: After a long term of prognostic standpoint, PIK3CA mutations discussed as a major target for various
cancers. These PIK3CA mutations were found in various exon including 1,2,4,6,7,9,13,18 and 20 which may
be a cause of different cancers such as breast, colon, ovarian, gastric, brain, lung etc. In clinical trials these mutations
still remain question marks for presence or absence to the scientist regarding future perspective. The opinion
of these studies is to development of more specific inhibitors of PI3K pathway which produce tremendous impact
on various cancers developed due to PIK3CA mutations.
