Researchers validate molecular signature used to predict benefit from radiation therapy
The technology, which identifies radiosensitivity and radioresistance, opens the door to biologically guided radiation therapy
- Date : 21 Aug 2012
- Topic : Breast cancer
Researchers at Moffitt Cancer Center, working with colleagues in Sweden, the Netherlands and Puerto Rico, have validated a radiosensitivity molecular signature that can lead to better radiation therapy decisions for treating patients with breast cancer. The results appeared in a recent issue of Clinical Cancer Research, a journal of the American Association for Cancer Research.
The study examined patients with breast cancer who had been treated with radiation therapy and demonstrated that a radiosensitivity molecular signature could predict clinical outcomes exclusively in patients treated with radiation therapy. The radiosensitivity molecular signature, used by the research team, has previously been tested and validated for rectal, oesophageal, and head and neck cancers. The technology, which identifies radiosensitivity and radioresistance, opens the door to biologically guided radiation therapy and offers the potential for better outcomes.
A radiosensitivity molecular signature was developed by using a systems-biology strategy
Developing a radiosensitivity predictive assay has been a goal of radiation biology for decades, according to Dr Javier Torres-Roca, member of the Experimental Therapeutics programme at Moffitt. This effort supports the emphasis on personalised medicine, where the goal is to use molecular signatures to guide therapeutic decisions.
Approximately 60% of all cancer patients receive radiation therapy during their treatment. Yet until now, no molecular diagnostic or biomarker of radiosensitivity had been developed to predict its benefit.
The radiosensitivity molecular signature was developed based on gene expression for 10 specific genes and a linear regression algorithm. It was developed in 48 cancer cell lines using a systems-biology strategy focused on identifying biomarkers for cellular radiosensitivity. This study validated radiosensitivity molecular signature benefit when researchers found that radiosensitive breast cancer patients had an improved five-year, relapse-free survival when compared to radioresistant patients.
The most extensively validated molecular signature in radiation oncology
The study validated radiosensitivity molecular signature in 503 patients in two independent data sets. The researchers have validated radiosensitivity molecular signature in five independent cohorts in total 621 patients, so this latest validation study makes this technology the most extensively validated molecular signature in radiation oncology.
The successful transition from applying the technology to cell lines and to patient application also suggests that the biological basis of cellular radiosensitivity is conserved between cell lines and patients and also across epithelial tumours.
The researchers propose that the radiosensitivity molecular signature is a predictive biomarker of radiation therapy for patients with breast cancer. This novel biomarker provides an opportunity to integrate individual tumour biology with clinical decision-making in radiation oncology.
The research was supported in part by the USA National Cancer Institute, part of the National Institutes of Health, through the grant number R21 CA101355 and R21 CA135620; the National Functional Genomics Center; and the State of Florida Bankhead-Coley Foundation (09BB-22).
The radiosensitivity molecular signature technology is owned by Moffitt and licensed to Cvergenx, Inc., an advanced cancer molecular diagnostics company committed to delivering personalised radiation therapy to cancer patients.
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