Current clinical pharmacology
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The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor activity in patients with BRCA deficient breast and ovarian cancers, and in patients with triple-negative breast cancer. In this review we aim to summarize the most recent advances in the development of PARP inhibitors, with a focus on the clinical data.
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Curr Clin Pharmacol · Aug 2010
ReviewMolecular targeted therapy in prevalent tumors: learning from the past and future perspectives.
Important advances have been achieved with molecular targeted agents in clinical oncology. Breast, colon, and lung cancer, are now commonly treated with a combination of chemotherapy and targeted agents. In this article the authors discuss the limitations of targeted therapy development, failures of previous studies, and possible strategies for an intelligent drug development. Initial attempts to block mTOR in breast cancer, the magnitude of benefit obtained with anti-EGFR therapy in lung cancer, and the narrowing use of anti-EGFR therapy in colon cancer based on KRAS status are discussed.