Survival of the Healthiest

Photo: Imaging of the tissue of a breast

Fighting cancer withhout destroying
healthy tissue - the researchers
tested a new approach in mice;
© NCI Visuals Online

An international research team led by Professor Cohen-Armon of Tel-Aviv University found that potent phenanthridine derived polyADP-ribose polymerase (PARP) inhibitors that were originally designed to protect cells from cell-death under stress conditions (for instance stroke or inflammation), efficiently eradicate breast cancer cells without impairing normal proliferating cells, such as human epithelial cells, nor normal non-proliferating cells, such as neurons and cardiomyocytes.

Human cancers depending on a constitutive activity of externally regulated kinase (ERK) were examined. The rationale for testing PARP inhibitors in these cancers was the recently disclosed up-regulation of ERK signals in the nucleus by activated PARP-1. However, other mechanisms are apparently involved. The phenanthridine PJ-34 caused a permanent G2/M cell-cycle arrest and cell death within 48 to 72 hours in breast cancer cells. In contrast, normal proliferating cells overcame the imposed G2/M cell-cycle arrest within twelve hours, survived and continued to proliferate.

In vivo, PJ-34 prevented the development of the breast cancer cells in nude mice without affecting their growth, development or behaviour. According to Cohen-Armon, "This research provides a new therapeutic approach for a selective eradication of abundant human cancers."

Other PARP inhibitors were recently proved efficient only for treating relatively rare hereditary human cancers developed in individuals with an impaired DNA repair (BRCA gene mutation). However, in the current research, breast cancer cells lacking the BRCA mutation were efficiently eradicated.

MEDICA.de; Source: BioMed Central