It’s the dog days of summer and time for some meaty controversy to read!
For the longest time there have been several cancer types which have been incredibly difficult to treat therapeutically.
Metastatic melanoma and non-small cell lung cancer (NSCLC) both used to be in this category, as did glioblastoma and advanced pancreatic ductal adenocarcinoma (PDAC).
We have made great strides in changing the face (and more importantly outcomes!) for people with both metastatic melanoma and lung cancer, so what’s happening on the pancreatic cancer front?
The last two years gave certainly thrown up a series of disappointing clinical trial readouts such as RESOLVE, HALO–301, CanStemIIIP, and SEQUIOA, for example, where in each and every case the findings favoured the control arm of gemcitabine plus nab-paclitaxel over the experimental arm in terms of improving survival. Not one of them was able to raise the bar and show a significant improvement over standard therapy, which is pretty disappointing.
So what can be done to change the face of PDAC?
If we want to improve further then we need to go back to basics and enhance not only our understanding of the funadamental biological mechansisms and processes, but also the models we use to interrogate the systems involved.
In this post, we look at six key new areas of research in PDAC and explain what we’ve learned and why they matter if we are to see new therapeutic developments arise from the ashes of the past…
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As we continue to follow the emerging KRAS niche longitudinally, we can easily imagine the kind of roller coaster ride that ensues with new product development in oncology R&D.
Early last year we posted an interview with Mirati’s CEO, Dr Chuck Baum, discussing their selective KRASG12C inhibitor. A year on much has happened in the intervening time – additional competitors and potential collaborators have entered the clinic, a few mechanisms of resistance identified, and numerous combination partners have been suggested. The company have also aired their own phase 1 data and new trials are expected to open during 2020.
This time around we talk to both Dr Baum and the company’s CSO, Dr James Christensen, about their experiences in the front line in terms of translating the preclinical data into clinical trials, their thoughts on important scientific data as well as the competition, and what to watch out for going forward.
This field is going to not only go fast judging by the emerging research published to date, but it’s also going to get way more complicated than many observers realise.
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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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In Pharmaland it is frequently the case that once a target has been validated there’s always new developments in the form of novel agents that emerge, as well as emerging new related targets to consider.
Standing from the KRAS crowd
Here we combine an update on some new market entrants in the KRAS niche with an expert interview discussing how to address a known area of acquired resistance that has recently been highlighted. Naturally, that also brings with it yet more novel targets and potential combination strategies that may need to be considered by players in this space.
Yes, KRAS G12C is now a rapidly evolving area with multiple players and many moving parts, whereas even just back in January this year many observers saw it as a three horse race – think again, it’s much deeper and broader than that somewhat naive hypothesis already!
As usual, we follow these races longitudinally with regular updates and explain why new scientific findings need to be considered if we are to make a difference in the clinic with future combination strategies.
Are you ready for the latest game of 3D chess?
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