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see also:
Table 1. DNA Repair Pathways
(Lynch Syndrome, BRCA 1/2, FANC, ATM, MYH ;
Table 2. PARP Inhibitor Clinical Trials; Other Potential Synthetic Lethal Strategies for PARP Inhibitors.....
Conclusions:
"The synthetic lethal targeting of DNA repair pathways, as exemplified by PARP inhibitors, in cancers bearing HR DNA repair defects is showing considerable potential for delivering selective tumor cell kill while sparing normal cells, and offers a scientifically rational and potentially broad clinical application in oncology.64 Several challenges related to the development of these inhibitors remain, including the identification of robust predictive biomarkers of HR deficiency in cancers. The dissection of the underlying mechanisms of PARP inhibitor resistance and establishment of optimal drug combinations and strategies for chemoprophylaxis with these therapies remain high priorities. It is important to be aware that different PARP inhibitors may have varying potencies on individual members of the PARP superfamily and also affect other targets, resulting in distinct toxicity and efficacy profiles. In the future, it is envisioned that this tumor-specific synthetic lethal strategy with PARP inhibitors may potentially be utilized against cancers with similar molecular defects but diverse anatomical origins.118 Such a paradigm shift in drug discovery may crucially bring us closer to our ultimate goal of personalized medicine."
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