PARP Inhibitors for the Treatment of Ovarian Cancer.

The standard of treatment for advanced ovarian cancer is represented by optimal surgical debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive treatment strategy, almost 75% of patients relapse or progress and are therefore candidates for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An interesting approach to improve outcomes of these patients has been developed in the last decade, in BRCA-related ovarian cancer.

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time?

Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment.

BRCA1/2 genetic background-based therapeutic tailoring of human ovarian cancer: hope or reality?

Ovarian epithelial tumors are an hallmark of hereditary cancer syndromes which are related to the germ-line inheritance of cancer predisposing mutations in BRCA1 and BRCA2 genes. Although these genes have been associated with multiple different physiologic functions, they share an important role in DNA repair mechanisms and therefore in the whole genomic integrity control. These findings have risen a variety of issues in terms of treatment and prevention of breast and ovarian tumors arising in this context.

Loss of BRCA1 function increases the antitumor activity of cisplatin against human breast cancer xenografts in vivo.

Background: Previous reports suggested a central role of BRCA1 in DNA-damage repair mechanisms elicited by cell exposure to anti-tumor agents. Here we studied if BRCA1-defective HCC1937 or BRCA1-reconstituted HCC1937/(WT)BRCA1 human breast cancer xenografts (HBCXs) generated in SCID mice were differentially sensitive to cisplatin (CDDP) in vivo and we investigated potential molecular correlates of this effect.

Results: CDDP induced almost complete growth inhibition of BRCA1-defective HBCXs, while BRCA1-reconstituted HBCXs were only partially inhibited.