KRAS is the most commonly mutated gene in human cancers.  Until recently (late 2013) this was thought to be an "undruggable" target.  It is mutated in around 30% of all human cancers combined but is mutated in around 90% and 40% of pancreatic and lung cancers respectively.

 

The protein product of the KRAS gene (known as K-Ras) acts as a molecular switch.  In its active (or ON) state, it promotes cell division.  In its inactive (or OFF) state it does not promote cell division.  Mutations in the KRAS gene can cause the K-Ras protein to become stuck in the ON state irrespective of upstream growth signals.  This provides excessive signals for cell division and can help to accelerate cancerous growth.   

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Image sourced from http://humana-portal.dnadirect.com/content/physician-site/kras/index.html

 

In 2013, researchers developed small molecules which specifically bind to a mutant form of the K-Ras thereby inhibiting it.  The molecules do not bind to the wild type (or normal) K-Ras so they have the key advantage of being a targeted cancer therapy. (Ostrem et al., Nature 2013).  This research could pave the way for clinical trials of these molecules and if these are successful, the drugs could be available as a viable treatment option by the early 2020s.

 

The precise catalyst event put forward here is the point at which any such drug formally receives approval (e.g. by the FDA) following successful phase III clinical trials. 

​
Any such treatment has significant implications for cancer mortality as KRAS mutated cancers are highly represented by pancreatic and lung cancers which presently have very poor five year survival rates.

 

Source:

Jonathan M. Ostrem, Ulf Peter, Martin L. Sos,  James A. Wells & Kevan M. Shokat  

K-Ras (G12C) inhbitors allosterically control GTP affinity and effector interactions. Nature (2013)