Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors

Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer.

1. Öberg K, Knigge U, Kwekkeboom D et al. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23(Suppl 7):vii124–30. 2. Raymond E, Dahan L, Raoul JL et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N England J Med 2011; 364: 501–513. 3. Yao JC, Shah MH, Ito T et al. Everolimus for...

PARP inhibitors in breast cancer.

The therapeutic implications of DNA damage in cancer therapy have long been appreciated and form the basis of many successful cytotoxic chemotherapy and radiotherapy treatment strategies. A novel class of DNA repair defect targeted therapeutics that inhibit poly (ADP-Ribose) polymerase (PARP) are being rapidly developed in breast cancer based on exciting preliminary clinical activity as single ...

PARP Inhibitors for Cancer Therapy

Rucaparib is an inhibitor of nuclear poly (ADP-ribose) polymerases (inhibition of PARP-1 > PARP-2 > PARP-3), following a similar drug, Olaparib. It disrupts DNA repair and replication pathways (and possibly transcription), leading to selective killing of cancer cells with BRCA1/2 mutations. Rucaparib is approved for recurrent ovarian cancers with germline or somatic mutations in BRCA1/2.

PARP Inhibitors in Ovarian Cancer

Loss of INPP4B causes a DNA repair defect through loss of BRCA1, ATM and ATR and can be targeted with PARP inhibitor treatment

Treatment options for ovarian cancer patients remain limited and overall survival is less than 50% despite recent clinical advances. The lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described as a tumor suppressor in the PI3K/Akt pathway with loss of expression found most pronounced in breast, ovarian cancer and melanoma. Using microarray technology we identi...