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Researchers to Identify Genetic Biomarkers for Aggressive Breast Cancer

The Avon Foundation for Women recently awarded a $300,000 grant to Dolores Di Vizio, MD, PhD, associate professor in the Department of Surgery and the Department of Pathology and Laboratory Medicine and a member of the Cancer Biology and Urologic Oncology Research Programs at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute to advance scientific research in aggressive breast cancer.

Di Vizio will collaborate with the Cedars-Sinai Women’s Cancer Program to investigate biomarkers in patient blood samples that may identify individuals with aggressive breast cancer. Biomarkers are genes or other molecules that can indicate a person’s predisposition to specific medical conditions.

Research findings have the potential to create a novel standard of care and a new source of biomarkers. The possible new source of biomarkers, known as large oncosomes, are tumor-derived vesicles that transmit signaling complexes between cell compartments, providing valuable insight into the progression of disease. Findings may also help researchers and clinicians predict the aggressiveness of breast cancer earlier in the diagnostic process.

“This kind of research is the essential foundation to get us to our real goal, which is to improve diagnostic and prognostic capabilities and find effective treatments for breast cancer,” said Di Vizio. “With this study, we hope to identify previously unrecognized large oncosomes as potential biomarkers in advanced tumors that can be visualized, quantified and isolated using methods easily translatable to the clinic.”

Funding from the Avon Foundation for Women, a nonprofit organization and longtime supporter of Cedars-Sinai, will provide an opportunity for researchers to further spearhead new technologies, therapies and surgical interventions that may provide better patient outcomes, beginning at diagnosis.

Working with Di Vizio to provide these advancements is collaborator Beth Y. Karlan, MD, director of the Women’s Cancer Program, director of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology, the Cedars-Sinai Board of Governors Chair in Gynecologic Oncology and the director of the Cedars-Sinai Gilda Radner Hereditary Cancer Program.

“I’m excited to be a collaborator on this research study, as it holds promise to provide tangible improvements in earlier diagnostics and detection in aggressive breast cancer and is perfectly aligned with the program goals of the Cedars-Sinai Women’s Cancer Program,” said Karlan. “This Avon Foundation for Women grant will further our program’s commitment to studying cancer biology, developing new approaches to early detection and preventing and improving cancer survival for all patients.”

This is the first study on large oncosomes analyses in patients with breast cancer. Pilot funding for this grant is supported by the Martz Breast Cancer Discovery Fund.

Source: EurekAlert!

Team Finds Markers Related to Ovarian Cancer Survival and Recurrence

Researchers at the University of Illinois have identified biomarkers that can be used to determine ovarian cancer survival and recurrence, and have shown how these biomarkers interact with each other to affect these outcomes. Their findings appear in the journal PLOS ONE.

Researchers try to find molecules called biomarkers that help determine a person’s likelihood of getting a disease or, if they have already been diagnosed, how far the disease has advanced. Genes, transcription factors and microRNAs are often used as biomarkers because these molecules can be heralds of disease or portents of susceptibility.

Genes are segments of DNA that code for proteins or other molecules that perform the functions of the cell. Transcription factors regulate these genes by binding to specific DNA sequences, preventing or inducing the genes to be “expressed” at higher or lower levels. MicroRNAs, as their name suggests, are small RNA molecules that regulate an intermediate stage of gene expression. Transcription factors and microRNAs also can regulate each other.

The relationships among transcription factors, microRNAs and target genes can be visualized as interconnected networks. These intricate webs are often used to determine how diseases such as cancer proceed. Analyzing how these networks function in cancer can offer insight into how tumor cells proliferate and differentiate, undergo (or resist) programmed cell death, and how likely they are to become invasive.

According to the American Cancer Society, an estimated 22,240 women will be diagnosed with ovarian cancer in 2013, and 14,230 will die of the disease; this makes ovarian cancer the fifth most common cause of cancer death in women.

The high prevalence of ovarian cancer and ovarian cancer deaths in the U.S. prompted U. of I. animal sciences professor Sandra Rodriguez-Zas and doctoral researcher Kristin Delfino to search for biomarkers associated with ovarian cancer survival and recurrence.

“We knew that there are specific biomarkers that have been associated with ovarian cancer, but we were looking at whether we could more accurately predict survival or age at cancer recurrence considering hundreds of interacting biomarkers simultaneously,” Rodriguez-Zas said.

The team used data from the Cancer Genome Atlas, which contains information about ovarian cancer patients’ age, survival, cancer recurrence, treatment, tumor stage, tumor grade and genomic expression. The researchers then performed statistical tests to tie these factors to patients’ survival time, measured in months from diagnosis to death, and their recurrence time, measured in months from diagnosis to recurrence.

“The networks change for people who have different rates of survival, so we looked at what’s being expressed in high-survival patients compared to what’s being expressed in low-survival patients,” Delfino said.

The team was able to confirm the association of 21 microRNAs with ovarian cancer. They also found 838 target genes and 12 transcription factors associated with ovarian cancer survival and 734 target genes and eight transcription factors associated with ovarian cancer recurrence.

“We were able to find many biomarkers that held the same relationship with survival no matter the cancer treatment, as well as some that were unique in their relationship with survival depending on the treatment the patient had received,” Rodriguez-Zas said.

Delfino said that a network-based approach is more predictive of ovarian cancer survival and recurrence than a single-molecule-based perspective.

“We took a step back and looked at everything from a network point of view instead of just individually to see how the components interacted with each other and how the biomarkers were associated with ovarian cancer survival and recurrence,” Delfino said.

“This demonstrated that the consideration of networks of microRNAs, transcription factors, and target genes allows us to identify reliable indicators of cancer survival and recurrence and serves as the basis for effective prognostic tools,” Rodriguez-Zas said.

Delfino believes this study opens the door to the creation of less invasive diagnostic tests and more specialized treatment options for women with ovarian cancer.

“In the future we’d like to be able to just take a little sample of your DNA and be able to tell you what’s going to happen, what we can do to prevent it, and how to cut cancer off before it ever reaches that point,” Delfino said. “Everyone is different, and hopefully, we will be able to specify the treatment that will best treat the individual patient.”

Study: Transcription Factor-MicroRNA-Target Gene Networks Associated with Ovarian Cancer Survival and Recurrence

Source: University of Illinois at Urbana-Champaign

Skuldtech and AB Science Announce the Identification of New Predictive Markers for Pancreatic Cancer Survival Associated with Masitinib Treatment

Skuldtech, a genomic and pharmacogenomic company specialized in developing diagnostic tests, and AB Science (NYSE Euronext – FR0010557264 – AB), a pharmaceutical company specialized in developing tyrosine kinase inhibitors, announce the discovery of a new set of blood markers predictive of a higher survival rate in pancreatic cancer patients. Skuldtech and AB Science plan to exploit these new markers for commercialization of a future companion test associated with masitinib, a molecule developed by AB science for treating pancreatic cancer.

Scientists Unravel Resistance to Breast Cancer Treatment

Tamoxifen – used alongside traditional chemotherapy and radiotherapy – blocks the female hormone oestrogen that, in certain breast cancers, is required by the tumour to grow; it has been shown to improve cancer survival rates by up to one third.

Major Lung Cancer Screening Trial announced by the NHS in Scotland using an innovative blood test, EarlyCDT–Lung

Sir Harry Burns, The Chief Medical Officer for Scotland recently announced that Scotland will conduct a major screening trial for lung cancer using EarlyCDT–Lung – a simple blood test that detects cancer at its earliest stages of development. EarlyCDT–Lung has been available in the US for more than two years and has been shown to detect early and late stage cancers in research studies as well as in clinical use. An audit of more than 1,500 patients has been overseen by independent leading cancer clinicians and confirms the test performs in the clinic as expected. The objective of this randomised prospective trial is to ascertain the cost–effectiveness of EarlyCDT-Lung in screening high risk patients. Initial calculations from an independent firm of health economists in Boston show that it should be highly cost effective and reduce lung cancer mortality. Lung cancer survival rates in the UK have remained very poor (9% five year survival) for decades.