Discovering the Secrets of Brain Tumors

Physicians decide how to treat brain cancer in part based on what a patient’s tumor looks like under the microscope. But while the microscope can help classify a tumor, it cannot always reveal the molecular changes that drive the disease. And in an era of molecularly targeted therapies, this is what physicians and patients increasingly want to know.

Molecular markers have been identified and even genomic tests have been developed for breast and other common cancers, but progress has been slower in brain cancer. Obtaining the tumor tissue needed for molecular studies is difficult, and hundreds, if not thousands, of samples are needed to capture the genetic diversity of brain cancer.

Nonetheless, there is reason for optimism. Some of the first genomic studies of cancer included surveys of brain tumors, and for the first time, several clinical trials are enrolling patients based on tumor markers, such as combined deletions on chromosomes 1 and 19.

A database being developed by NCI and its partners around the country could also help move the field toward more individualized care. The Glioma Molecular Diagnostic Initiative (GMDI) is collecting and integrating molecular, genetic, and clinical data on hundreds of patients with gliomas, the most common type of brain tumor.

Changing the System

The March 1 issue of Cancer Research includes one of the first publications using the study’s database. The researchers propose a new classification system for gliomas based on tumor gene activity. While the results are considered preliminary, they illustrate the promise of an approach that seeks to integrate different types of information from patients with the disease, the researchers said. “Unlike the standard classification system for gliomas, we came up with a system that is based purely on biology,” said lead investigator Dr. Howard A. Fine, chief of NCI’s Neuro-Oncology Branch in the Center for Cancer Research. “The results confirm and extend the findings of smaller glioma classification studies published previously,” he added. Collectively, these studies show that there are subtypes of brain tumors defined not by their appearance under the microscope, but rather by the molecular pathways that are altered in tumors, said Dr. Mark Gilbert, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center, who was not involved in the research. “These studies all have the same goal,” Dr. Gilbert continued. “For a hundred years we’ve made treatment decisions on the basis of looking at brain tumor tissue under the microscope. Yet we know that two patients can have very different outcomes even though their tumors look identical, so it would be helpful if we could figure out the pathways that made the cancers different.”

Clinical Genomics

Created to help attain that goal, GMDI has enrolled more than 800 patients with gliomas at 14 institutions around the country. A tumor sample collected during surgery for each patient is sent to NCI for molecular analysis. Clinical information on each patient is then linked to molecular and genetic descriptions of the tumor in a public database called REMBRANDT (Repository of Molecular Brain Neoplasia Data). “We have built the largest cancer clinical genomics database for any tumor type, let alone an uncommon type such as glioma,” said Dr. Fine. In the Cancer Research study, the researchers used 159 gliomas from GMDI to develop an algorithm that assigns gliomas to six subtypes under two groups, glioblastomas and oligodendrogliomas. They validated the algorithm in three additional data sets, totaling nearly 700 gliomas. The results confirm what physicians have always known—that some patients will do better than others for reasons that may not be understood, said Dr. Michael Prados, director of translational research in neuro-oncology at the University of California, San Francisco Comprehensive Cancer Center. He also leads a consortium that provided some of the annotated tumor samples used in the analysis. “If we really want to change the outcomes for patients, then we need therapies that address changes in particular pathways,” added Dr. Prados. “We don’t have those therapies now, so the challenge going forward is: How will we use this information to make a difference in patients therapeutically?”

Exploring the Biology

As a next step, Dr. Fine’s group is characterizing the biology of the tumors to inform the development of new therapies. Until very recently, most patients with brain cancer received the same toxic drugs. But with a growing pipeline of molecularly targeted cancer drugs, physicians can start to evaluate these agents rationally in clinical trials.

Given that the most common subtypes may include only about 10 percent of all tumors, the selection of patients for these trials will be critical. A drug may perform poorly in a trial of unselected patients, and therefore could be discarded, even though it may be very effective for a specific subset of patients. “For prognostic purposes, for drug development, and for the design of future clinical trials, we really need to be able to group brain tumors according to their underlying biology,” said Dr. Fine.

The genome surveys published last year and a recent follow-up report about relatively common mutations in brain tumors have set the stage for more individualized approaches to the disease. And while much more work remains to be done, everyone in the field seems to be moving in the same direction. “Information is power, and these studies are all expanding the knowledge base,” said Dr. Prados. “This will let us develop therapies for patients in a more specific way.” —Edward R. Winstead

Henry Ford Hospital and Rosetta Genomics to Develop MicroRNA-based Diagnostics for Brain Cancer

The American Cancer Society Estimates Approximately 20,000 Patients are Diagnosed With Brain Cancer Each Year in the U.S.

January 14, 2008: 08:30 AM EST

REHOVOT, Israel and NORTH BRUNSWICK, New Jersey, January 14 /PRNewswire-FirstCall/ -- Rosetta Genomics, Ltd. , a leader in the development of microRNA-based diagnostics and therapeutics, announced today it has signed a collaboration agreement with the Henry Ford Health System in Detroit, Michigan, to develop microRNA-based diagnostics and prognostics for brain cancer. The Henry Ford Hospital is one of the world's leading research centers for brain cancer.

Under the collaboration, the parties will conduct a genome-wide molecular analysis of human brain cancer tumors to identify unique microRNA biomarkers that have diagnostic and prognostic potential. Upon receipt of the results from this analysis, Rosetta Genomics will use its proprietary microRNA extraction technologies to perform a microRNA analysis from Formalin Fixed Paraffin Embedded (FFPE) samples received from Henry Ford Hospital.

"The goal of our collaborations with the leading cancer research centers is to seek new indications for our microRNA-based diagnostics," said Amir Avniel, President and CEO of Rosetta Genomics. "Together with Henry Ford Hopsital's leading brain cancer researchers, we believe we will be able to leverage the potential microRNAs hold as biomarkers to develop diagnostic and prognostic tools for this difficult disease."

"There is great unmet medical need for improved diagnostics in identifying and treating patients with brain cancer," said Chaya Brodie, Ph.D., and Tom Mikkelsen, M.D. of the department of neurosurgery at Henry Ford Hospital. Dr. Brodie is Director of the William and Karen Davidson Laboratory of Cell Signaling & Tumorigenes and neuro-oncologist Dr. Mikkelsen is co-director of the Hermelin Brain Tumor Center. "A significant advantage of using microRNAs as biomarkers, is that they do not degrade when the tumor sample is stored as an FFPE block. As FFPE blocks can be stored at room temperature, these sample types are readily available and allow us to conduct retrospective studies. Through these studies, we can identify microRNA diagnostic and prognostic biomarkers, such as for disease staging, response to treatment, and risk of recurrence. Combining Rosetta Genomics' proprietary technologies for microRNA research and its experience in this field with our expertise in brain cancer is a good starting point for this important project."

About MicroRNAs

MicroRNAs (miRNAs) are recently discovered, naturally occurring small RNAs that act as master regulators and have the potential to form the basis for a new class of diagnostics and therapeutics. Since many diseases are caused by the abnormal activity of proteins, the ability to selectively regulate protein activity through microRNAs could provide the means to treat a wide range of human diseases. In addition, microRNAs have been shown to have different expression in various pathological conditions. As a result, these differences may provide for a novel diagnostic strategy for many diseases.

About Henry Ford Hospital

Henry Ford Hospital is a 903-bed tertiary care hospital, education and research complex in Detroit's New Center Area. The Hermelin Brain Tumor Center at Henry Ford Hospital focuses on brain and spine tumors and is considered one of the largest neuro-oncology centers in the nation. It also houses one of the most comprehensive brain tumor research labs and biorepository in the country. The Center continues to focus on novel investigations to help control brain tumor growth and spread, including molecular targeted therapy; gene therapy and anti-angiogenesis therapy.

About Rosetta Genomics

Rosetta Genomics is a leader in the development of microRNA-based diagnostics and therapeutics. Founded in 2000, the company's integrative research platform combining bioinformatics and state-of-the-art laboratory processes has led to the discovery of hundreds of biologically validated novel human microRNAs. Building on its strong IP position and proprietary platform technologies, Rosetta Genomics is working to develop a full range of microRNA-based diagnostic and therapeutic products, focusing primarily on cancer and various women's health indications. The company expects its first microRNA-based diagnostic tests to be launched during 2008.

Forward-Looking Statement Disclaimer

Various statements in this release concerning Rosetta's future expectations, plans and prospects, including without limitation, statements relating to the role of microRNAs in human physiology and disease, the potential of microRNAs in the diagnosis and treatment of disease, and our ability to successfully develop a microRNA-based diagnostic test for brain cancer constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including risks related to: Rosetta's approach to discover and develop novel diagnostics and therapeutic products, which is unproven and may never lead to marketable products; Rosetta's ability to fund and the results of further pre-clinical and clinical trials; Rosetta's ability to obtain, maintain and protect the intellectual property utilized by Rosetta's products; Rosetta's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Rosetta's ability to obtain additional funding to support its business activities; Rosetta's dependence on third parties for development, manufacture, marketing, sales, and distribution of products; Rosetta's ability to successfully develop its product candidates, all of which are in early stages of development; Rosetta's ability to obtain regulatory approval for products; competition from others using technology similar to Rosetta's and others developing products for similar uses; Rosetta's dependence on collaborators; and Rosetta's short operating history; as well as those risks more fully discussed in the "Risk Factors" section of Rosetta's Annual Report on Form 20-F for the year ended December 31, 2006 as filed with the Securities and Exchange Commission. In addition, any forward-looking statements represent Rosetta's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Rosetta does not assume any obligation to update any forward-looking statements unless required by law.

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