The study, entitled Single-strand DNA-binding protein hSSB1 is critical for genomic stability has identified and characterised a novel human single-stranded DNA binding protein (hSSB1). hSSB1 is an upstream sensor in the double-strand break response pathway - double strand DNA breaks are lethal if they are not repaired.

"Chemotherapy, which is highly toxic, is currently the only option for most cancer patients. Not only does chemotherapy kill off the cancerous cells, it also kills off healthy cells, leading to severe nausea, fatigue, hair loss and in some cases death," said co-author Dr Liza Cubeddu from the University of Sydney's School of Molecular and Microbial Biosciences.

hSSB1 is recruited to sites of DNA breaks where it co-localizes with other repair proteins. Cells depleted in hSSB1 are hypersensitive to ionizing radiation, which causes double-strand breaks that are not repaired efficiently.

"hSSB1 is a prerequisite for cancer cells to survive, normal cells can function without it," said Dr Cubeddu. "Developing a drug that can target the hSSB1 gene means that you can destroy cancerous cells while leaving healthy cells intact. This could revolutionise how cancers are treated and potentially put an end to aggressive DNA damaging chemotherapies and radiotherapy treatments," she said.

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To test their reasoning they conducted a second experiment by crossing mice carrying the prostate-specific IGF-1R knockout alleles with transgenic mice that develop spontaneous prostate cancer when p53 and select other genes are compromised. The results were as predicted: Prostate epithelial-specific deletion of IGF-1R facilitated the emergence of aggressive prostate cancer in the genetically-engineered tumor prone mice.

Published in the May 1 edition of Cancer Research, the study supports a critical role for IGF-1R signaling in prostate tumor development and identifies an important IGF-1R-dependent growth control mechanism, according to the authors. Title of the paper is "Conditional deletion of insulin-like growth factor-1 receptor in prostate epithelium."

"If our predictions hold true, tumor cells with intact p53 may show the best response to therapy targeting the IGF-1R signal, however when p53 is not functioning normally, response to this therapy may not be as expected," said Greenberg, the study's corresponding author and a member of the Hutchinson Center's Clinical Research Division.

Greenberg's message to clinicians who administer IGF-R1 therapy: "We're all hoping for good results but let's proceed with caution."

A search of the database for clinical trials registered with the National Cancer Institute found 18 trials in process that use therapies to inhibit IGF-R1. None of them include a tumor's p53 status as a criterion for recruiting research participants, said Greenberg.

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