Innovative algorithm spots interactions lethal to cancer

Tel Aviv University research identifying cancer-busting 'genetic partners' can personalize cancer treatment

2014-09-03

(Press-News.org) Despite the revolutionary biotechnological advancements of the last few decades, an ideal anti-cancer treatment — one that's immediately lethal to cancer cells, harmless to healthy cells, and resistant to cancer's relapse — is still a dream.

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 last week in the highly prestigious 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.

INFORMATION: American Friends of Tel Aviv University supports Israel's leading, most comprehensive and most sought-after center of higher learning, Tel Aviv University (TAU). Rooted in a pan-disciplinary approach to education, TAU is internationally recognized for the scope and groundbreaking nature of its research and scholarship — attracting world-class faculty and consistently producing cutting-edge work with profound implications for the future. TAU is independently ranked among the world's top universities and #1 in Israel. It joins a handful of elite international universities that rank among the best producers of successful startups.

ELSE PRESS RELEASES FROM THIS DATE:

Transplanted stem cells help prevent bladder fibrosis after spinal cord injury

2014-09-03

Putnam Valley, NY. (Sept. 3, 2014) – A team of researchers from Korea and Canada have found that transplantation of B10 cells (a stable immortalized human bone marrow derived –mesenchymal stem cell line; B10 hMSC) directly into the bladder wall of mice modeled with spinal cord injury (SCI) helped inhibit the development of bladder fibrosis and improved bladder function by promoting the growth of smooth muscle cells in the bladder. The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub ...

Penn study: Sepsis patients fare better in hospitals with higher case volumes

2014-09-03

PHILADELPHIA – Patients with sepsis, one of the most time-sensitive and hard-to-detect illnesses in medicine, are more likely to survive the life-threatening condition when treated at a hospital that sees a higher volume of sepsis cases. New research from the Perelman School of Medicine at the University of Pennsylvania shows a clear relationship between hospitals that treat the most cases of severe sepsis and lower rates of inpatient deaths among those patients. The study, led by David F. Gaieski, MD, an associate professor of Emergency Medicine at Penn, is published online ...

Pesticide risk assessments seen as biased

2014-09-03

In the October issue of BioScience, a group of ecotoxicologists argue that the US Environmental Protection Agency's (USEPA) current practices for evaluating pesticide safety are inadequate and likely to result in decisions biased toward industry interests. In their article, Michelle Boone of Miami University and her colleagues note that most pesticide toxicity tests used in risk assessments are conducted by pesticide manufacturers themselves, which the authors believe can result in untenable conflicts of interest. Moreover, rigid inclusion criteria often mean that potentially ...

Seizures and sudden death: When SUMO 'wrestles' potassium channels

2014-09-03

A gene crucial for brain and heart development may also be associated with sudden unexplained death in epilepsy (SUDEP), the most common cause of early mortality in epilepsy patients. Scientists at The University of Texas MD Anderson Cancer Center have created a new animal model for SUDEP and have shown that mice who have a partial deficiency of the gene SENP2 (Sentrin/SUMO-specific protease 2) are more likely to develop spontaneous seizures and sudden death. The finding occurred when observing mice originally bred for studying a link between SENP2 deficiency and cancer. "SENP2 ...

Researchers unlock new mechanism in pain management

2014-09-03

It's in the brain where we perceive the unpleasant sensations of pain, and researchers have long been examining how calcium channels in the brain and peripheral nervous system contribute to the development of chronic pain conditions. Neuroscientist Gerald Zamponi, PhD, and his team at the University of Calgary's Hotchkiss Brain Institute have discovered a new mechanism that can reverse chronic pain. Using an animal model, their research has found that pain signals in nerve cells can be shut off by interfering with the communication of a specific enzyme with calcium ...

Changing temperature powers sensors in hard-to-reach places

2014-09-03

A centuries-old clock built for a king is the inspiration for a group of computer scientists and electrical engineers who hope to harvest power from the air. The clock, powered by changes in temperature and atmospheric pressure, was invented in the early 17th century by a Dutch builder. Three centuries later, Swiss engineer Jean Leon Reutter built on that idea and created the Atmos mechanical clock that can run for years without needing to be wound manually. Now, University of Washington researchers have taken inspiration from the clock's design and created a power ...

Tweets during 2013 Colorado floods gave engineers valuable data on infrastructure damage

2014-09-03

Tweets sent during last year's massive flooding on Colorado's Front Range were able to detail the scope of damage to the area's infrastructure, according to a study by the University of Colorado Boulder. The findings can help geotechnical and structural engineers more effectively direct their reconnaissance efforts after future natural disasters—including earthquakes, tsunamis and tornadoes—as well as provide them data that might otherwise be lost due to rapid cleanup efforts. "Because the flooding was widespread, it impacted many canyons and closed off access to communities ...

Galapagos invasion is global warning

2014-09-03

A new study led by a PhD researcher at The University of Western Australia has revealed that parts of the iconic Galapagos Islands have been overrun by invasive plants from other parts of the world. "People may be shocked that a place considered so iconic for biodiversity is so overrun with weeds in some areas despite ongoing control effort by National Park rangers, but this is really a global story," lead author from the UWA School of Plant Biology Mandy Trueman said. The results published in the open access journal Neobiota confirm that in the humid highland part ...

Peptoid nanosheets at the oil-water interface

2014-09-03

From the people who brought us peptoid nanosheets that form at the interface between air and water, now come peptoid nanosheets that form at the interface between oil and water. Scientists at the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have developed peptoid nanosheets - two-dimensional biomimetic materials with customizable properties - that self-assemble at an oil-water interface. This new development opens the door to designing peptoid nanosheets of increasing structural complexity and chemical functionality for a broad ...

How well does bariatric surgery work?

2014-09-03

SEATTLE—The number of bariatric surgeries done each year in the United States has ballooned. Now, in an August 27 state-of-the-art review in The BMJ and a September 3 editorial in JAMA, David Arterburn, MD, MPH, weighs the evidence on the benefits and risks of the various types of this surgery. "It's critical that we find effective—and cost-effective—ways to treat severe obesity," said Dr. Arterburn, an associate investigator at Group Health Research Institute, a Group Health physician, and an affiliate associate professor of medicine at the University of Washington School ...

LAST 30 PRESS RELEASES:

Novel radiation therapy QA method: Monte Carlo simulation meets deep learning for fast, accurate epid transmission dose generation

A 100-fold leap into the unknown: a new search for muonium conversion into antimuonium

A new approach to chiral α-amino acid synthesis - photo-driven nitrogen heterocyclic carbene catalyzed highly enantioselective radical α-amino esterification

Physics-defying discovery sheds new light on how cells move

Institute for Data Science in Oncology announces new focus-area lead for advancing data science to reduce public cancer burden

Korea University College of Medicine successfully concludes the 2025 Lee Jong-Wook Fellowship on Infectious Disease Specialists Program

Girls are happiest at school – for good reasons

Researchers from the University of Maryland School of Medicine discover genetic ancestry is a critical component of assessing head and neck cancerous tumors