#Alexander skwr update

Tutt A, Robson M, Garber JE etВ al (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. N Engl J Med 361:123вЂ“134ДЇong PC, Yap TA, Boss DS etВ al (2010) Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. Cancer Res 66:8109вЂ“8115ДЇong PC, Boss DS, Yap TA etВ al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. McCabe N, Turner NC, Lord CJ etВ al (2006) Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Mendes-Pereira AM, Martin SA, Brough R etВ al (2009) Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. Turner NC, Reis-Filho JS, Russell AM etВ al (2007) BRCA1 dysfunction in sporadic basal-like breast cancer. Press JZ, De Luca A, Boyd N etВ al (2008) Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities. Turner N, Tutt A, Ashworth A (2004) Hallmarks of вЂBRCAnessвЂ™ in sporadic cancers. Nature 434:913вЂ“917ДЇarmer H, McCabe N, Lord CJ etВ al (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Cancer Treat Rev 31:603вЂ“617Д«ryant HE, Schultz N, Thomas HD etВ al (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Madhusudan S, Middleton MR (2005) The emerging role of DNA repair proteins as predictive, prognostic and therapeutic targets in cancer. Plummer R, Jones C, Middleton M etВ al (2008) Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors.

Poly (ADP-ribose) polymerase (PARP) inhibitors.

#Alexander skwr update

The aim of this chapter is to provide an update on the current status of single agent PARP inhibitor clinical trials. At least five agents have now entered late stage phase III drug development in an effort to gain regulatory approval and advance the field of PARP inhibitor therapy. While there have indeed been some setbacks in the development of this class of drugs, major concerns with regards to PARP inhibitor specificity, patient selection or toxicity have or are being addressed.

Several phase I and II trials have reported PARP inhibitors to be efficacious with favorable side effect profiles. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic cancers with defective HRR pathways. with PARP inhibitor monotherapy for tumours with germline mutations in BRCA1 and BRCA2.

One of the most novel potential uses of PARP inhibitors is as single agents exploiting the concept of вЂњsynthetic lethalityвЂќ in settings where the DNA homologous recombination repair (HRR) pathway is compromised-e.g. Several drugs targeting poly (ADP-ribose) polymerase (PARP) enzymes are in clinical development.