Pathways to success with small molecule developments
It always amuses me when people describe the small molecule space in lymphomas as ‘neat and ordered’ when in reality, it is anything but…
After all, not all patients respond initially, some cannot tolerate the side effects, and additional mutations can be acquired in response to therapy inducing acquired resistance and sometimes more aggressive disease results.
How do we go about addressing all of these issues in order to improve outcomes further?
We can certainly get a few ideas from the early stage pipelines being evaluated, as well as from the kind of combination regimens currently being developed. What do the results show?
Then there’s a raft of quite unrelated agents which might be competitive and could usurp existing approaches should they move earlier up in the treatment paradigm. Plenty of Pharma execs have certainly been caught out in the past not keeping their eyes on the right eight ball.
In our latest ASH20 Preview we highlight a few intriguing abstracts to watch out for at the forthcoming meeting this weekend…
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It’s the dog days of summer and yet there’s a lot happening on the DDR front from multiple angles.
After a short break from science, this makes now a really good time to reflect and take stock in order to explore some of the key issues facing the field, especially in terms of future combination approaches.
Research that’s appearing now may influence future trial designs – always a nagging worry in Pharmaland that the standard of care can change before you even get your own phase 3 readout! No one likes to be pipped to the post, after all.
With the early WEE–1 news this week and a raft of new PARP readouts, there is much to discuss and also plenty of nuance and subtlety to consider carefully because what looks obvious at first blush may not actually be the case based on prior evidence that many will have forgotten about.
So grab a cup of iced coffee and shades and settle down under your sunbrellas for a pleasant and easy to read review of the various trials, settings, combinations and DDR pathway considerations…
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DNA Damage Repair (DDR) has come a long way over the last decade or so from preclinical development through clinical trials, including some notable failures along the way. What began initially with PARP inhibitors, has now expanded into other related targets in the pathway, including ATM/ATR, WEE–1, Chk1/2, DNA-PK, and even Fanconi anemia genes such as FANCA/BC/D1, BRIP1 and PALB2, which are considered an indication of BRCAness where there is also chromosomal instability and homologous recombination.
Top 10 DDR targets and molecules at AACR19
At AACR last week, there was plenty to learn about in the ever-expanding DDR niche in terms of new data from a relatively new target such as DNA-PK to updated clinical data on WEE–1 and Chk1 inhibition to early data on PARP in a new tumour type to add to the growing list of ovarian, breast, and prostate cancers that are impacted by DDR therapies.
Included in this post are 10 key targets or molecules in the DDR niche that are of potential interest to readers – we explain why we included them and why the data matters.
Here we take a look at the highlights that we came across in this mini review, which should be useful preparation ahead of yet more clinical data likely being presented at ASCO and ESMO later this year.
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