Can we break through the barriers of a hostile tumour microenvironment?
Who would have thought that after 30 years of no new therapies that urothelial carcinomas would suddenly be almost constantly in the spotlight with enticing words like cancer immunotherapy, biomarkers, tumour microenvironment, translational immunology etc?
And yet it has happened – with a lot more to come in this highly competitive niche too.
Prior to AACR in Chicago, we highlighted TGFβ in our Preview series as an important emerging target that is gathering attention and may be relevant in tumour types, such as urothelial carcinoma and ovarian cancer.
After the meeting, Dr Paul Rennert (CSO, Aleta Biotherapeutics) noted:
I don’t disagree with either of these sentiments – there was a reason we interviewed a lot of NK cell enthusiasts recently and we have since been rolling out our thought leader mini-series focused on TGFβ. Yesterday, we kicked off with perspectives from an academic researcher active in this field and tomorrow will showcase some practical clinical perspectives.
On deck today, we have a interview with a research scientist who has conducted both basic and translational work for a discussion about how he sees the learnings that have arisen from bench to bedside and back again.
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The convergence between targeted therapies and immunotherapies with genomics has already started in many areas of cancer research – we can imagine the intersections more as a Venn diagram than as separate entities these days.
Lobster pots on the shore
While former graveyards of R&D such as metastatic melanoma and lung cancer have seen a dramatic revival in positive trials over the last five years, things have languished somewhat in other areas.
Womens cancers such as high grade serous ovarian cancer (HGSOC) and triple negative breast cancer (TNBC) have seen some new developments with the advent of PARP inhibitors as monotherapy or maintenance, but there is still a ways to go in terms of overcoming resistance and improving outcomes further.
You might be puzzled what on earth lobster pots have to do with cancer research? In short it’s an apt analogy from life because while there is much promise in the right situation (under the sea in a good situation), they can also look like a helpless mess (abandoned on the shore). Oncology R&D is a bit like that too and finding the right situation viz molecule development and clinical trial design, not to mention discontinuation is very similar in that respect too.
In our latest AACR18 Preview, we take a look at an underappreciated oncology drug class and look at the opportunities for future combinations that may take a few readers by surprise…
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Two of the most intriguing developments in cancer research over the last 5 years have been checkpoint blockade and CAR T cell therapies. There’s no doubt that they work – in some patients – or that toxicities can be challenging to manage at times, but what has been very interesting to me has been physician reactions to the rise of immunotherapies.
There has been much noise about biomarkers, including whether they work or not in this niche, as well as how do we go about selecting patients for therapies and combinations?
Ultimately, immunotherapies will be no different from targeted therapies in that we need to better understand the underlying biology in order to move forward beyond the low hanging fruit and figure out how we can best select appropriate therapy for each individual based on their particular characteristics.
The worry that many researchers have is that we could end up making the same mistakes with immunotherapies as targeted therapies, i.e. treat them in a broad fashion akin to throwing mud at the wall. Indeed, some companies are already doing this, much to the consternation of the research community.
So how do we go about doing things better and thinking more strategically about what needs to be done?
Up next is the first in a two-part interview series with a global thought leader who is a scientist-clinician with expertise in both immunology and oncogenic pathways. What does he have to say about where we are now and importantly, what does the future hold?
This is the penultimate article in our coverage from the Triple meeting in Munich, held in November 2016.
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