The past year has seen hype and hope over targeting KRAS mutant cancers and many challenges still remain to be addressed. We’ve seen the emergence of selective G12C inhibitors, as well as others targeting SOS1:RAS upstream and even related pathways to address cross-talk such as SHP2 and ULK1, for example. The oncology R&D ecosystem is beginning to motor again as new competitors start entering the niche.
Riding the KRAS wave
To put things into broader perspective, however, despite all the positive news in lung cancer, consider the colorectal carcinoma data was less impressive than lung because of more complex, heterogeneous disease.
Meanwhile, Lilly recently announced the discontinuation of their selective G12C inhibitor, LY3499446, due to adverse toxicity, so clearly it is not all going to be plain sailing in this landscape!
Let’s also not forget the G12C mutation is not the only viable target in this context. People with advanced lung cancer can also present with one or more of several co-occurring mutations such as the serine/threonine kinase 11 gene (STK11) and kelch like ECH associated protein 1 gene (KEAP1), for example.
Unfortunately those presenting with both STK11 and KEAP1 mutations – independent of KRAS status – often have a poorer prognosis and there remains an unmet medical need for effective new treatments.
In this fourth postcard in our summer mini-series on the potential of immunometabolism for cancer immunotherapy, we’re taking a look at a novel way to target KRAS mutant lung cancer and, in particular, those with an STK11 and KEAP1 mutation who tend to do poorly on current therapies.
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This is the second postcard in our mini-series on the emerging field of immunometabolism and the translational potential for cancer new product development.
Over the course of three weeks, we’ll be sharing six postcards from our journey, three of which are based around interviews with scientists at the forefront of research in this niche.
What did we learn about immunometabolism at AACR20?
In this latest post we’re taking a look at some of the signals at this year’s virtual AACR annual meeting, which as usual had a wealth of data on offer, offering as it does a window into the future of cancer drug development.
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Not in San Diego – In normal times of past years, the AACR annual meeting generally takes place once a year in April before we haed onto oter events such as ASGCT, ASCO, and EHA. In these abnormal times in the middle of the COVID–19 pandemic, however, the virtual event was split into two, with the first online event in April covering mainly early clinical data, and now we get to learn from the meaty scientific presentations, which are being highlighted this week.
A network of mutations, tumour suppresses, metabolic and immune processes, as well as other hidden factors can unexpectedly impact therapy outcomes in NSCLC
We have a lot of translational researchers reading BSB, so I wanted to kick off the first of the AACR Virtual Meeting series with a scientific focus, which is likely of interest to many for a number of obvious reasons.
The good news is this a topic we have covered before and so there’s already a body of work to build on for reference since this latest round of information not only adds to what we know, but also highlights some additional unknown unknowns yet to be elucidated.
The dichotomy is an essential part of the very essence and fun of science – the more we think we know, the less we really know in practice, especially as the various layers of the onion get gradually peeled off over time.
This latest review mixes up translational research with clinical research…
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First in class or best in class?
Which paths will ultimately lead to success with novel targeted therapies?
Ah this question often seems a perennial one to consider at AACR annual meetings – and this year is no different in this respect.
Personally, to me, it doesn’t really matter what you claim aspirationally based on preclinical or even early phase 1 dose escalation data because… a lot can happen between then and later registrational studies.
Think about it carefully – weak efficacy, wrong tumour selection or setting, adverse event profiles, even narrow therapeutic windows can all too soon interfere and play havoc like a wrecking ball with many a well intended clinical program, especially once you start looking at combination strategies!
No, it’s not as easy as it looks sometimes.
In our latest AACR Preview series, we take a look at a number of targeted agents in development, many aimed at novel targets at are not run-of-the mill…
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In wave 3 of the immuno-oncology surge things have slowed down, partly due to a raft of combination trials yet to read out and partly because the reality has finally hit that tumour heterogeneity means there will be variable patient responses.
Just getting from room to room on time can be a real challenge with 40,000 other people present!
This complexity can come about in many forms… immunosuppression, alterations in gene functions, resistance and immune escape, to name a few.
If we want to help more people respond to these therapies then before we can rush headlong into another round of combination trials, we first have to go back to looking carefully at the underlying biology of the diseases and listen to what the patient’s tumours are telling us in order to fix things.
To accomplish this feat requires considerable time, energy, effort, and a lot of bioinformatics.
In this post we explore five key talks that highlight different aspects of biomarkers of response and mechanisms of resistance. From there, we may see additional validation and prospective testing to determine how best to segment people so that they have the greatest chance of responding to the therapy administered.
One thing that most people don’t have these days is time, which is how we can help you because here’s a handy short cut to finding out more about five complex and diverse areas on biomarkers or IO resistance quickly and easily…
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The huge pile of interesting scientific papers yet to be read seems to breed overnight and one constantly feels like they’re 2,000 articles behind, even with spending Friday mornings attacking them with gusto.
This was as true in my PhD days as it is now. For a scientist, these represent a lifeline and an important necessity, rather than a luxury.
In the last journal club posting we covered some hot topics in cancer immunotherapy, so this one covers a very different topic, namely targeted therapies.
It’s a good time for a new journal club post, where we tackle some of the recent published literature in oncology and highlight some important new findings that could have an impact on cancer research and development.
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