Putting the rap on Akt

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• The protein kinase Akt is frequently activated in diverse cancers, contributing to apoptosis resistance.
• This activation is controlled by the interplay between the PI3-K oncogene and the PTEN tumor suppressor.
• Aberrant Akt activation is linked to oncogenic mutations like HER-2/neu amplification and BCR/ABL fusion.

Purpose of the Study:

• To review the mechanisms controlling Akt activation in cancer.
• To elucidate the antiapoptotic functions of activated Akt.
• To discuss therapeutic strategies targeting the Akt pathway.

Main Methods:

• Review of existing literature on Akt signaling in cancer.
• Analysis of molecular mechanisms underlying Akt activation and function.
• Discussion of therapeutic implications of targeting Akt.

Main Results:

• Activated Akt confers resistance to apoptosis via inhibition of Bad, downregulation of death receptors, and enhanced glycolysis.
• Increased glycolysis, a hallmark of malignancy, aids in cancer diagnosis and staging.
• Specific oncogenic mutations drive Akt activation, essential for their transforming activity.

Conclusions:

• Akt signaling is a critical mediator of cancer development and survival.
• Understanding Akt regulation provides insights into therapeutic vulnerabilities.
• Rapamycin and analogs show promise as antineoplastic agents, particularly in Akt-activated tumors.