Shifting the balance of mitochondrial apoptosis: therapeutic perspectives

Simone Fulda

doi:10.3389/fonc.2012.00121

Abstract

Signaling via the intrinsic (mitochondrial) pathway of apoptosis represents one of the critical signal transduction cascades that control the regulation of cell death. This pathway is typically altered in human cancers, thereby providing a suitable target for therapeutic intervention. Members of the Bcl-2 family of proteins as well as cell survival signaling cascades such as the PI3K/Akt/mTOR pathway are involved in the regulation of mitochondria-mediated apoptosis. Therefore, further insights into the molecular mechanisms that form the basis for the control of mitochondria-mediated apoptosis will likely open new perspectives to bypass evasion of apoptosis and treatment resistance in human cancers.

Highlights

Simone Fulda*Reviewed by: Boris Zhivotovsky, Karolinska Institutet, Sweden Shazib Pervaiz, National University of Singapore, Singapore
Programmed cell death is an ancient, evolutionary highly conserved program that exists in every cell to execute cell death upon appropriate stimulation (Lockshin and Zakeri, 2007)
The phosphatidylinositol 3 -kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling cascade belongs to the critical survival programs that are typically overactivated in human cancers and can promote cell survival by inhibiting the mitochondrial pathway of apoptosis (Parcellier et al, 2008)

Summary

Simone Fulda*

Reviewed by: Boris Zhivotovsky, Karolinska Institutet, Sweden Shazib Pervaiz, National University of Singapore, Singapore. Signaling via the intrinsic (mitochondrial) pathway of apoptosis represents one of the critical signal transduction cascades that control the regulation of cell death. This pathway is typically altered in human cancers, thereby providing a suitable target for therapeutic intervention. Members of the Bcl-2 family of proteins as well as cell survival signaling cascades such as the PI3K/Akt/mTOR pathway are involved in the regulation of mitochondria-mediated apoptosis. Further insights into the molecular mechanisms that form the basis for the control of mitochondria-mediated apoptosis will likely open new perspectives to bypass evasion of apoptosis and treatment resistance in human cancers

INTRODUCTION

Mitochondrial apoptosis and cancer therapy

CONCLUSIONS