Posts Tagged ‘american’

Innovative algorithm spots interactions lethal to cancer

But a concept called “synthetic lethality” holds great promise for researchers. Two genes are considered synthetically lethal when their combined inactivation is lethal to cells, while inhibiting just one of them is not. Synthetic lethality promises to deliver personalized, more effective, and less toxic therapy. If a particular gene is found to be inactive in a tumor, then inhibiting its synthetic lethal partner with a drug is likely to kill only the cancer cells, causing little damage to healthy cells.

While this promising approach has been widely anticipated for almost two decades, its potential could not be realized due to the difficulty experimentally identifying synthetic lethal pairs in cancer. Now new research published in the journal Cell overcomes this fundamental hurdle and presents a novel strategy for identifying synthetic lethal pairs in cancer with the potential to bust cancer cells.

Tel Aviv University researchers have developed a computational data-driven algorithm, which identifies synthetic lethal interactions. In their comprehensive, multidisciplinary study, Dr. Eytan Ruppin of TAU’s Blavatnik School of Computer Science and the Sackler School of Medicine and Ms. Livnat Jerby-Arnon of TAU’s Blavatnik School of Computer Science worked together with other researchers from TAU, The Beatson Institute for Cancer Research (Cancer Research UK), and the Broad Institute of Harvard and MIT.

Taking cancer personally

Analyzing large sets of genetic and molecular data from clinical cancer samples, the scientists were able to identify a comprehensive set of synthetic lethal pairs that form the core synthetic lethality network of cancer. They have demonstrated for the first time that such a network can be used to successfully predict the response of cancer cells to various treatments and predict a patient’s prognosis based on personal genomic information.

“We started this research from a very simple observation: If two genes are synthetically lethal, they are highly unlikely to be inactive together in the same cell,” said Dr. Ruppin. “As cancer cells undergo genetic alterations that result in gene inactivation, we were able to identify synthetic lethal interactions by analyzing large sets of cancer genetic profiles. Genes that were found to be inactive in some cancer samples, but were almost never found to be inactive together in the same sample, were identified as synthetically lethal.”

The crux of the study, according to Ms. Jerby-Arnon, is the synergy between the computational research and the ensuing experiments, conducted at the Beatson Institute and the Broad Institute, to verify the predictive power of the new algorithm.

A road to new therapies

In addition to their promising role in tailoring personalized cancer treatment, the synthetic lethal pairs discovered may also be used to repurpose drugs, which are currently used to treat other non-cancer disorders, to target specific cancer types. “We applied our pipeline to search for drugs that may be used to treat certain forms of renal cancer. We identified two such drugs, currently used to treat hypertension and cardiac dysrhythmia, that may be quite effective,” said Dr. Ruppin. “Experiments in cell lines performed by the Gottlieb lab at the Beatson Institute support these findings, and we are now working on additional validations in mice.”

The researchers are hopeful that their study will help boost the experimental detection of synthetic lethality in cancer cells and offer further insight into the unique susceptibilities of these pathological cells. “In this study, we have demonstrated the clinical utility of our framework, showing that it successfully predicts the response of cancer cells to various treatments as well as patient survival,” said Ms. Jerby-Arnon. “In the long-run, we hope this research will help improve cancer treatment by tailoring the most effective treatment for a given patient.”

The researchers are in the process of forming experimental and clinical international collaborations to test key emerging leads for novel drug targets and drug repurposing.

source : http://www.sciencedaily.com/releases/2014/09/140903163532.htm

Increase seen in use of double mastectomy, although not associated with reduced death

Randomized trials have demonstrated similar survival for patients with early-stage breast cancer treated with breast-conserving surgery and radiation or with mastectomy. However, previous data show increasing use of mastectomy, and particularly bilateral mastectomy (removal of both breasts) among U.S. patients with breast cancer. Evidence for a survival benefit with this procedure appears limited to rare patient subgroups. “Because bilateral mastectomy is an elective procedure for unilateral breast cancer [in one breast] and may have detrimental effects in terms of complications and associated costs as well as body image and sexual function, a better understanding of its use and outcomes is crucial to improving cancer care,” according to background information in the article.

Allison W. Kurian, M.D., M.Sc., of the Stanford University School of Medicine, Stanford, Calif., and colleagues used data from the California Cancer Registry from 1998 through 2011 to compare the use of and rate of death after bilateral mastectomy, breast-conserving therapy with radiation, and unilateral mastectomy (removal of one breast).

The analyses included 189,734 patients. The researchers found that the rate of bilateral mastectomy increased from 2.0 percent in 1998 to 12.3 percent in 2011, an annual increase of 14.3 percent. The increase in bilateral mastectomy rate was greatest among women younger than 40 years: the rate increased from 3.6 percent in 1998 to 33.0 percent in 2011, increasing by 17.6 percent annually. Use of unilateral mastectomy declined in all age groups

Bilateral mastectomy was more often used by non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute-designated cancer center; in contrast, unilateral mastectomy was more often used by racial/ethnic minorities and those with public/Medicaid insurance.

Compared with breast-conserving surgery with radiation, bilateral mastectomy was not associated with a mortality difference, whereas unilateral mastectomy was associated with higher mortality.

“In a time of increasing concern about overtreatment, the risk-benefit ratio of bilateral mastectomy warrants careful consideration and raises the larger question of how physicians and society should respond to a patient’s preference for a morbid, costly intervention of dubious effectiveness,” the authors write.

“These results may inform decision-making about the surgical treatment of breast cancer.”

Editorial: Contralateral Prophylactic Mastectomy: Is It a Reasonable Option?

In an accompanying editorial, Lisa A. Newman, M.D., M.P.H., of the University of Michigan, Ann Arbor, discusses the issues involved with the use of contralateral prophylactic mastectomy (risk-reducing mastectomy for the unaffected breast).

“The need for patients to be accurately informed regarding safe and oncologically acceptable treatment options is indisputable. The dense fog of complex emotions that accompanies a new cancer diagnosis can impair the ability to process this information. Patients should be encouraged to allow the intensity of these immediate reactions to subside before committing to mastectomy prematurely. Physicians should not permit excessive treatment delays to compromise outcomes, but the initial few weeks surrounding the diagnosis are more effectively utilized by time invested in patient education and procedures that contribute to comprehensive treatment planning as opposed to hastily coordinating impulsive, irreversible surgical plans.”

source : http://www.sciencedaily.com/releases/2014/09/140902171150.htm

Recommendations for prostate cancer active surveillance

With active surveillance, patients undergo regular visits with prostate-specific antigen (PSA) tests and repeated prostate biopsies rather than aggressive treatment. It is distinguished from watchful waiting, in which treatment for localized disease is withheld and palliative treatment for systemic disease is initiated.

“Active surveillance is an important management option for men with low-risk prostate cancer,” says lead author Mahul Amin, MD, FCAP, Chair, Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA. “Vital to this process is the critical role pathologic parameters play in identifying appropriate candidates for active surveillance.”

Dr. Amin spearheaded the team that highlighted the pathologic parameters key for the successful identification of patients likely to succeed with active surveillance. The key parameters, at a general level, address: •Sampling, submission, and processing issues in needle biopsies used to diagnose prostate cancer •Tumor extent in needle biopsies •Biopsy reporting for all and special cases •Gleason scores, the system for grading prostate cancer tissue based on how it looks under a microscope •Precision medicine markers •Other pathologic considerations

The team further concluded that the key parameters to be reported by the surgical pathologists: 1) need to be reproducible and consistently reported and 2) highlight the importance of accurate pathology reporting.

Recommendations from the United States Preventive Services Task Force, an independent group of national experts in prevention and evidence-based medicine, and randomized trials have drawn attention to overtreatment of localized, low-risk prostate cancer. PSA screening and changing consensus on PSA testing practices are among the many factors that contribute to prostate cancer’s overdiagnosis and overtreatment.

The pathology recommendations are included in the Archives article: The Critical Role of the Pathologist in Determining Eligibility for Active Surveillance as a Management Option in Patients with Prostate Cancer: Consensus Statement with Recommendations Supported by the College of American Pathologists, International Society Of Urological Pathology, Association of Directors of Anatomic and Surgical Pathology, the New Zealand Society of Pathologists, and the Prostate Cancer Foundation.

source : http://www.sciencedaily.com/releases/2014/08/140826100651.htm