Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘KRAS mutations’

Attention on small molecule inhibitors – after being in the doldrums for a while – seem to be making a comeback over the last year with much attention focused on a few companies developing new selective agents in specialised niches.

Time for a KRAS spring clean!

One such space is KRAS inhibition. Not just in terms of direct or indirect inhibition, but also with regards to tackling acquired resistance mechanisms such as SHP2.  While there has been quite the frenzy over what Amgen, Mirati, Revolution Medicine and a few others are all doing, other companies are quietly getting on with the business of producing some nice work and will soon be ready for the off.

In our latest review we explore some of the factors involved, which companies will need to be concerned about going forward, especially in the context of future combination strategies.

In solid tumours, with targeted therapies the winners are not always the ones who reached the market first, but rather the crafty ones who optimise the combination strategies and become ingrained in protocols across multiple situations.

Here we look at one of the hidden gems in the KRAS space and explore what it does, why it’s important and how it might fit in.  We also include a company interview with a scientist who gets the broader implications…

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Fall in Boston during the AACR-NCI-EORTC Triple meeting

After recent updates on targeting KRASG12C and HRAS, let’s not forget that there are plenty of other elements of the RAS pathway that can be considered, not least is upstream receptor kinases such as EGFR and sideways to SHP2.

What happens when those worlds collide?

Quite a bit it would seem.

If we want to seriously impact patient outcomes for the better then we need to explore rational combination approaches.

Here’s one way to do it…

Please note that this is an early target with not very many competitors, so there’s plenty that can happen here on multiple fronts!

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Henry Moore sculpture – looks like a protein binding pocket!

Cambridge, UK – It’s somewhat ironic that we headed across town today to chat with one of the world’s leading cell biologists on MYC and RAS with a post on KRASG12C inhibitors almost ready in the bag. More on that interview in a future mini-series.

There are a number of nuances and subtleties involved in this niche, which have been somewhat lost in the frantic hype over hope melêe of late.

This review discussing KRAS and various other co-mutations such as LKB1/STK11 is a long and thorough one,, and perhaps rather contrarian in nature.

That said, I do feel that it is very important to highlight a lot of issues that are being ignored in the rush to declare the latest expected winners and losers or even potential blockbusters, if the breathless signals are to be believed.

If nothing else, there are certainly several key issues that could have a bearing on the clinical results in patients that are worthwhile highlighting for discussion and adding to the watch list because some of these factors may well take time to develop.

This is one of those ‘Ground Control to Major Tom – take your protein pills and put your helmet on’ moments… Actually, I may well be needing the helmet as protection if the analysis and commentary turn out to be unpopular!!

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