Work

PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?

Year: 2006

Type: article

Abstract: Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment. It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers. However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice. Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed. Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive. These findings suggest that PARP inhibition may serve as an approach for the prevention of BRCA related breast cancer and may be useful in combination with other chemotherapeutic agents in the treatment of breast cancer.

Source: International Journal of Medical Sciences

DOI: 10.7150/ijms.3.117

Authors: Joseph A. De Soto, Chu-Xia Deng

Institutions: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

Language: English

Topic: PARP inhibition in cancer therapy

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,337