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PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications; the most important is the treatment of cancer.〔(【引用サイトリンク】title=ZDNet Healthcare )〕 Several forms of cancer are more dependent on PARP than regular cells, making PARP an attractive target for cancer therapy.〔(【引用サイトリンク】title=PARP Inhibitor and DNA Polymerase Repair - PARP Inhibitor )〕 〔(【引用サイトリンク】title=Development of PARP Inhibitors: An Unfinished Story )〕〔(【引用サイトリンク】title=PARP Inhibitors – More Widely Effective than First Thought )〕 PARP inhibitors appear to improve progression-free survival in women with recurrent platinum-sensitive ovarian cancer, as evidenced mainly by olaparib added to conventional treatment. In addition to their use in cancer therapy, PARP inhibitors are considered a potential treatment for acute life-threatening diseases, such as stroke and myocardial infarction, as well as for long-term neurodegenerative diseases. ==Mechanism of action== DNA is damaged thousands of times during each cell cycle, and that damage must be repaired. BRCA1, BRCA2 and PALB2 are proteins that are important for the repair of double-strand DNA breaks by the error-free homologous recombinational repair, or HRR, pathway. When the gene for either protein is mutated, the change can lead to errors in DNA repair that can eventually cause breast cancer. When subjected to enough damage at one time, the altered gene can cause the death of the cells. PARP1 is a protein that is important for repairing single-strand breaks ('nicks' in the DNA). If such nicks persist unrepaired until DNA is replicated (which must precede cell division), then the replication itself can cause double strand breaks to form.〔McGlynn, P. and Lloyd, B. "Recombinational Repair and Restart of Damaged Replication Forks." Nature Reviews, 2002, pp.859-870〕 Drugs that inhibit PARP1 cause multiple double strand breaks to form in this way, and in tumours with BRCA1, BRCA2 or PALB2 〔 mutations these double strand breaks cannot be efficiently repaired, leading to the death of the cells. Normal cells that don't replicate their DNA as often as cancer cells, and that lack any mutated BRCA1 or BRCA2 still have homologous repair operating, which allows them to survive the inhibition of PARP.〔N Engl J Med 361:123〕〔N Engl J Med 361:189〕 Some cancer cells that lack the tumor suppressor PTEN may be sensitive to PARP inhibitors because of downregulation of Rad51, a critical homologous recombination component, although other data suggest PTEN may not regulate Rad51.〔 Hence PARP inhibitors may be effective against many PTEN-defective tumours〔 (e.g. some aggressive prostate cancers). Cancer cells that are low in oxygen (e.g. in fast growing tumors) are sensitive to PARP inhibitors.〔http://discuss-cancer.com/2010/07/experimental-drug-may-work-in-many-cancers/〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「PARP inhibitor」の詳細全文を読む スポンサード リンク
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