Development of PI3K inhibitors: lessons learned from early clinical trials View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-03

AUTHORS

Jordi Rodon, Rodrigo Dienstmann, Violeta Serra, Josep Tabernero

ABSTRACT

The phosphatidylinositol 3-kinase (PI3K) pathway has an important role in cell metabolism, growth, migration, survival and angiogenesis. Drug development aimed at targetable genetic aberrations in the PI3K/AKT/mTOR pathway has been fomented by observations that alterations in this pathway induce tumour formation and that inappropriate PI3K signalling is a frequent occurrence in human cancer. Many of the agents developed have been evaluated in early stage clinical trials. This Review focuses on early clinical and translational data related to inhibitors of the PI3K/AKT/mTOR pathway, as these data will likely guide the further clinical development of such agents. We review data from those trials, delineating the safety profile of the agents--whether observed sequelae could be mechanism-based or off-target effects--and drug efficacy. We describe predictive biomarkers explored in clinical trials and preclinical mechanisms of resistance. We also discuss key unresolved translational questions related to the clinical development of inhibitors of the PI3K/AKT/mTOR pathway and propose designs for biomarker-driven trials to address those issues. More... »

PAGES

143

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nrclinonc.2013.10

    DOI

    http://dx.doi.org/10.1038/nrclinonc.2013.10

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031948211

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23400000


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