Going beyond PARP inhibitors to improve cancer outcomes
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.
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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