OVARIAN CANCER and US: BRCAness

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Showing posts with label BRCAness. Show all posts
Showing posts with label BRCAness. Show all posts

Wednesday, February 01, 2012

open access: PLoS ONE: BRCAness Profile of Sporadic Ovarian Cancer Predicts Disease Recurrence



Background

The consequences of defective homologous recombination (HR) are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways) could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes.

Objective

To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.

Results

High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04). Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03).

Conclusions

Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance.

Thursday, January 21, 2010

Jan 2009 full free access - Development of PARP inhibitors in oncology; Expert Opinion on Investigational Drugs + Expert Opinion



Note: highly technical but worth reviewing (BRCAness, sporadic, specific therapies (combination/single agent/+radiotherapy), those in clinical studies (Table 1),
differing cancers etc