Date published 
November 2011 

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The PI3K/Akt/mTOR Pathway: A Pipeline Analysis - Overview

 

Report Cover ImageAuthor: Peter Norman, MBA, PhD

The PI3K/Akt/mTOR signaling cascade serves many physiological and pathophysiological functions and is of major importance in a broad array of cancers. This has stimulated substantial interest in identifying and developing modulators of this pathway. This report includes:      

  • Pipeline reviews of PI3K, Akt, mTOR, and dual kinase inhibitors in development and an assessment of the current prospects for each approach
  • Role of the PI3K/Akt/mTOR cascade in various diseases and potential intervention strategies
  • Survey results offering unique insights into industry sentiment concerning development of inhibitors of this pathway
  • Profiles of selected companies that are targeting components of the PI3K signaling cascade, highlighting their distinct strategies
  • Significant licensing deals and acquisitions related to targeting the PI3K cascade
  • An overall assessment of progress in developing agents to modulate the PI3K/Akt/mTOR cascade and commercial prospects
  • Selected expert interviews on modulating the PI3K/Akt/mTOR cascade

In recent years it has become apparent that the activation of phosphatidylinositol 3-kinases (PI3Ks) initiates a complex sequence of intracellular events that include the activation of a number of other kinases, with Akt and mammalian target of rapamycin kinase (mTOR) both playing pivotal roles. The evidence for this PI3K cascade being heavily implicated in many types of cancer is very strong, with significant evidence for it also being important in other conditions, notably inflammatory diseases. This has led to extensive interest in the development of novel modulators of the activity of this cascade, primarily for the treatment of cancer.

The complexity of this cascade and the multiplicity of potential intervention points have prompted the structuring of The PI3K/Akt/mTOR Pathway: A Pipeline Analysis report to focus upon each of the main targets of this cascade in turn. The major components of the cascade are described in more detail before outlining potential intervention strategies. The evidence for the role of this cascade in various diseases is then considered, highlighting the limited scope for modulating it with currently approved therapies. The report considers inhibition of PI3K, Akt, mTOR, and dual kinases, highlighting the inhibitors that are in development and assessing the current prospects for each approach.

The interest in therapeutically exploiting the PI3K cascade has seen a number of companies emerge that focus either exclusively or significantly on targeting one or more of the components in this cascade. Their successes in identifying promising inhibitors have also seen a number of high-value deals, both co-development agreements and acquisitions, demonstrating the perceived value of the targets that such companies are pursuing. Specialist key players are profiled, highlighting their distinct strategies, and also the considerable interest seen in deal-making in this area.

Finally, we consider the prospects of commercial success for agents that modulate the PI3K/Akt/mTOR cascade. As more detailed clinical data become available, it can be expected that the level of interest in this cascade, and expectations of what can be achieved by its modulation, will be increased.

About the Author
Peter Norman, MBA, PhD,
is a pharmaceutical consultant and analyst based in Burnham Beeches, near Windsor, England, with specialist knowledge of the respiratory disease and inflammation markets. He has written and presented widely on various aspects of respiratory disease, generics, orphan drugs, and developments in therapeutic markets. Dr. Norman has over 20 years’ experience of the pharmaceutical industry in both R&D and competitive intelligence. His publications include many reviews and management reports, 16 original scientific papers, and 11 patents. Dr. Norman holds science degrees from Cambridge University and Brunel University plus an MBA degree from the Open University.