Onconase shows potential as radiation sensitizer for lung cancer treatment

Onconase (ranpirnase) could be a promising radiation sensitizer for lung cancer treatment, according to pre-clinical in vivo and in vitro data from a poster presentation at the 2008 American Association of Cancer Research (AACR) annual meeting in San Diego.

A natural protein isolated from the leopard frog, Onconase has been shown in the laboratory and clinic to target cancer cells while sparing normal cells. Onconase triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action, according to the Somerset, N.J.-based Alfacell.

In the poster "The inhibition of radiation repair by ranpirnase +/- I-buthionine sulfoximide on lung cancer," Intae Lee, MD, with the University of Pennsylvania, provided pre-clinical evidence that Onconase +/- I-buthionine sulfoximide significantly increased the radiation-induced growth delay of lung tumors in vivo without increases in skin reaction, compared to radiation alone.

Additionally, in vivo and in vitro data presented indicated that Onconase significantly increased apoptosis (programmed cell death) in several human non-small cell lung cancer (NSCLC) cell lines (A549, NCI-H1975 and HOP-62). Lee and his team of researchers also showed that the radiation repair mechanisms known as sub-lethal damage repair (SLDR) and potentially lethal damage repair (PLDR), which leads to radiation resistance in tumors, were significantly inhibited by Onconase in vitro.

"Our research suggests potential utility of Onconase as a radiotherapy enhancer for the treatment of NSCLC patients," said Lee. "It is important to overcome PLDR as it can ultimately lead to radiation resistance. One of our key findings is the inhibiting impact of Onconase on the PLDR mechanism, which is a pre-requisite to developing a radiotherapy enhancer."

Kuslima Shogen, Alfacell's CEO, added: "This work by Lee and his team provides further evidence of the potential for Onconase to mitigate the resistance that often develops in, and confounds the treatment of NSCLC."