After exploring a mechanistic approach and a tumour type as part of our AACR annual meeting coverage, in our third preview today we turn to look at a novel target.
This particular target hasn’t received much attention at all but this could well change in the future as some of the compounds move into the clinic.
There are a few important questions to consider:
- Who’s going to be first to evaluate in humans?
- Which tumour types will be optimal?
- Which combinations are likely to be synergistic, tolerable and effective?
- What path to market strategies will avoid the enrollment problems now that checkpoint blockade is becoming much more ubiquitous?
This is an interesting niche that may well evolve into a competitive landscape going forward.
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Over the last few years we have seen new therapies emerge for the treatment of advanced prostate cancer from immunotherapy to chemotherapy and second generation hormone therapies. Each of these has increased survival and outcomes. Along the way though, a host of other agents have fallen by the wayside with a raft of negative phase III trials that did not live up to their phase II promise. These include atrensentan, dasatinib, ipilimumab, lenalidomide and more recently, custirsen.
Much of the focus has, however, been on the hormonal drugs, abiraterone (Zytiga) and enzalutamide (Xtandi) in both the pre and post chemotherapy settings. One thing has become clear though – over time the responses attentuate as resistance sets in. This is very common with oral therapies.
Some big questions to consider here are:
- What causes it?
- How can we overcome adaptive resistance?
- Would combination approaches produce synergistic results?
- Or should we consider new targets with a different mechanism of action (MOA)?
The answers to these questions are now being eagerly explored through basic, translational and clinical research. I was very impressed with the quality of research and breadth of fresh ideas and approaches emerging from the SBUR, SUO and UOR sessions at AUA this year, including new combination trials already in the planning phase.
In the past, Bertrand Tombal (Belgium) talked about the Grand Cru year for clinical research in CRPC. In the future we may well look back at 2014 as a similar Grand Cru year for basic research for prostate cancer, if the findings translate to clinic. The bench-to-bedside process is very much alive and well in urologic research.
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