Year: 2012
Type: dissertation
Abstract: Breast cancer is the main cause of cancer death in women. Improved treatments, prevention programs and earlier detection are reducing the rate of death; however, there is still a high percentage of mortality by this cancer. Identification of novel targets to predict response to specific treatments is a key goal for personalizing breast cancer therapy and to improve survival. Few years ago, PARP inhibitors appeared as a promising therapy, particularly in BRCA-mutated cancers. However, there was a clear need to conduct further preclinical and translational work to improve the rational development of PARP inhibition in breast cancer.\n\n\t\t\t\t In this work we described PARP1 expression in breast tumour samples and characterized the effects of its inhibition in preclinical models. We found that nuclear PARP1 protein overexpression was associated with malignant transformation and poor prognosis in breast cancer. PARP1 overexpression was more common in triple negative subtype, but was also detectable in small subsets of estrogen receptor positive and HER2 positive breast cancers. In preclinical models, PARP1 played distinct roles in different molecular subtypes of breast cancer. Moreover, we described that olaparib (novel PARP inhibitor) had antitumour effects in different breast cancer subtypes, and its combination with trastuzumab (anti-HER2 antibody) enhanced the antitumour effects of this therapy.
Authors: G Lorena Parra, Jetzabel
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G4980488893
OpenAlex ID: W2262734151