New blood test could offer more tailored treatment of ovarian cancer

Researchers from The University of Manchester and The Christie NHS Foundation Trust — both part of Manchester Cancer Research Centre — say the test could be developed and used in hospitals within the next few years.

It would mean medics could see which patients could benefit from blood vessel-targeting drugs — such as bevacizumab — in addition to conventional therapy. Meanwhilehile others who are not going to benefit would be spared the time and side effects associated with having the drug.

The test would also help to reduce the cost to the NHS. Ovarian cancer has seen little increase in survival rates over the last few decades and scientists are seeking new treatment strategies to improve the standard approach of surgery and chemotherapy.

A recent advance has been to target the development of new blood vessels within the tumor — preventing the cancer from receiving the nutrients it needs to grow. Bevacizumab, one of the blood vessel-targeting drugs, has shown significant but modest improvements in patient survival so doctors are seeking ways to predict which patients are most likely to gain an advantage from this type of drug.

The research team looked at blood samples from patients enrolled in an international trial of bevacizumab. These patients received either standard chemotherapy treatment alone or chemotherapy plus the blood vessel-targeting drug.

Professor Gordon Jayson, Professor of Medical Oncology at The University of Manchester and Honorary Consultant at The Christie who jointly led the study, said: “We are keen to identify predictive biomarkers — measures that can indicate how well a patient will respond to treatment — so we can better target these drugs to patients most likely to benefit.”We investigated levels of a range of proteins in patients’ pre-treatment blood samples to see if any were associated with improved survival.”

The findings, published recently in the journal Clinical Cancer Research, show that two particular proteins — Ang1 and Tie2 — could be used in combination to predict patient response. Patients with high levels of Ang1 and low levels of Tie2 were most likely to benefit from bevacizumab.

Both these proteins are involved in controlling the formation of new blood vessels. Conversely, they found that patients with high levels of both proteins did not benefit from the additional drug.

Study co-author Professor Caroline Dive, from the Cancer Research UK Manchester Institute based at The University of Manchester, added: “We will now look to further explore the potential of using a blood test to personalise treatment for ovarian cancer patients.

Moving towards a more individualized treatment plan specific for each patient and their particular tumor is key to improving outcomes for patients while sparing those unlikely to benefit from potential side effects of therapy.”

source : http://www.sciencedaily.com/releases/2014/09/140905090419.htm

No association found between wearing bra, breast cancer

“There have been some concerns that one of the reasons why breast cancer may be more common in developed countries compared with developing countries is differences in bra-wearing patterns,” said Lu Chen, MPH, a researcher in the Public Health Sciences Division at Fred Hutchinson Cancer Research Center and a doctoral student in the Department of Epidemiology at the University of Washington School of Public Health. “Given how common bra wearing is, we thought this was an important question to address.

“Our study found no evidence that wearing a bra increases a woman’s risk for breast cancer. The risk was similar no matter how many hours per day women wore a bra, whether they wore a bra with an underwire, or at what age they first began wearing a bra,” said Chen.

“There has been some suggestion in the lay media that bra wearing may be a risk factor for breast cancer. Some have hypothesized that drainage of waste products in and around the breast may be hampered by bra wearing. Given very limited biological evidence supporting such a link between bra wearing and breast cancer risk, our results were not surprising,” Chen added.

According to the study authors, this study characterizes various bra-wearing habits in relation to breast cancer risk using a rigorous epidemiological study design. “The findings provide reassurance to women that wearing a bra does not appear to increase the risk for the most common histological types of postmenopausal breast cancer,” the authors noted.

Study participants were 454 women with invasive ductal carcinoma (IDC) and 590 women with invasive lobular carcinoma (ILC), the two most common subtypes of breast cancer, from the Seattle-Puget Sound metropolitan area; 469 women who did not have breast cancer served as controls. All women were postmenopausal, ages 55 to 74.

The researchers conducted in-person interviews and obtained information on demographics, family history, and reproductive history. They also asked a series of structured questions to assess lifetime patterns of bra wearing. Questions included age at which the study participant started wearing a bra, whether she wore a bra with an underwire, her bra cup size and band size, the number of hours per day and number of days per week she wore a bra, and if her bra-wearing patterns ever changed at different times in her life.

No aspect of wearing a bra was associated with an increased risk for either IDC or ILC.

source : http://www.sciencedaily.com/releases/2014/09/140905090615.htm

New gene mutations for Wilms tumor found

Wilms tumor is the most common childhood genitourinary tract cancer and the third most common solid tumor of childhood.

“While most children with Wilms tumor are thankfully cured, those with more aggressive tumors do poorly, and we are increasingly concerned about the long-term adverse side effects of chemotherapy in Wilms tumor patients. We wanted to know — what are the genetic causes of Wilms tumor in children and what are the opportunities for targeted therapies? To answer these questions, you have to identify genes that are mutated in the cancer,” said Dr. James Amatruda, Associate Professor of Pediatrics, Molecular Biology, and Internal Medicine at UT Southwestern and senior author for the study.

The new findings appear in Nature Communications. Collaborating with Dr. Amatruda on the study were UT Southwestern faculty members Dr. Dinesh Rakheja, Associate Professor of Pathology and Pediatrics; Dr. Kenneth S. Chen, Assistant Instructor in Pediatrics; and Dr. Joshua T. Mendell, Professor of Molecular Biology. Dr. Jonathan Wickiser, Associate Professor in Pediatrics, and Dr. James Malter, Chair of Pathology, are also co-authors.

Previous research has identified one or two mutant genes in Wilms tumors, but only about one-third of Wilms tumors had these mutations.

“We wanted to know what genes were mutated in the other two-thirds. To accomplish this goal, we sequenced the DNA of 44 tumors and identified several new mutated genes,” said Dr. Amatruda, who holds the Nearburg Family Professorship in Pediatric Oncology Research and is an Attending Physician in the Pauline Allen Gill Center for Cancer and Blood Disorders at Children’s Medical Center. “The new genes had not been identified before. The most common, and in some ways the most biologically interesting, mutations were found in genes called DROSHA and DICER1. We found that these mutations affected the cell’s production of microRNAs, which are tiny RNA molecules that play big roles in controlling the growth of cells, and the primary effect was on a family of microRNAs called let-7.”

“Let-7 is an important microRNA that slows cell growth and in Wilms tumors in which DROSHA or DICER1 were mutated, let-7 RNA is missing, which causes the cells to grow abnormally fast,” Dr. Amatruda said.

These findings have implications for future treatment of Wilms tumor and several other childhood cancers, including neuroblastoma, germ cell tumor, and rhabdomyosarcoma.

“What’s exciting about these results is that we can begin to understand what drives the growth of different types of Wilms tumors. This is a critical first step in trying to treat the cancer based on its true molecular defect, rather than just what a tumor looks like under a microscope,” Dr. Amatruda said. “Most importantly, we begin to think in concrete terms about a therapy, which is an exciting translational goal of our work in the next few years. This study also is a gratifying example of great teamwork. As oncologists, Dr. Chen and I were able to make rapid progress by teaming up with Dr. Rakheja, an expert pathologist, and with Dr. Mendell, a leading expert on microRNA biology.”

According to the American Cancer Society, an estimated 510 cases of Wilms tumor will be diagnosed among children in 2014. Also called nephroblastoma, Wilms tumor is an embryonal tumor of the kidney that usually occurs in children under age 5, and 92 percent of kidney tumors in this age group are Wilms tumor. Survival rates for Wilms tumor have increased from 75 percent in 1975-1979 to 90 percent in 2003-2009.

source : http://www.sciencedaily.com/releases/2014/09/140905113651.htm