Recent Developments in Anticancer Agents Targeting PI3K, AKT and mTORC1/2
Pp. 95-196 (102)
Irene Brana, Sara De Dosso, Rodrigo Dienstmann, Jordi Rodon, Josep Tabernero and Ben Markman
Inappropriate phosphoinositide 3-kinase (PI3K) signaling is one of the most
frequent occurrences in human cancer and is critical for tumor progression. Various
genetic mutations and amplifications have been described affecting key components of
this pathway, with implications for tumorigenesis and also for resistance to targeted
agents. Emerging preclinical research has significantly advanced our understanding of
the PI3K pathway and its complex downstream signaling, interactions and crosstalk.
This knowledge, combined with the limited clinical antitumor activity of mTOR
complex 1 inhibitors, has led to the development of rationally designed drugs targeting
key elements of this pathway, such as pure PI3K inhibitors (both pan-PI3K and
isoform-specific), dual PI3K/mTOR inhibitors, AKT inhibitors, and mTOR complexes
1 and 2 catalytic site inhibitors. This chapter will focus primarily on an analysis of
newly developed inhibitors of this pathway that have entered clinical trials, and recently
registered patents in this field.
AKT inhibitors, antineoplastic-agent, biological marker, clinical trial,
drug combination, drug design, drug mechanism, gene mutation, human,
mammalian target of rapamycin, mammalian target of rapamycin inhibitors,
molecularly targeted therapy, neoplasm, patents, phosphoinositide 3-kinase,
phosphoinositide 3-kinase inhibitors, pre-clinical experiment, pre- hyperglycemia,
proto-oncogene proteins c-AKT, rash.
Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology , P. Vall d'Hebron 119-129, 08035 Barcelona Spain.