Posts Tagged ‘dr-’

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

Preventing cancer from forming ‘tentacles’ stops dangerous spread

Roughly 2 in 5 Canadians will develop cancer in their lifetime, and one in four of them will die of the disease. In 2014, it’s estimated that nine Canadians will die of cancer every hour. Thanks to advances in medical research and care, cancer can often be treated with high success if detected early. However, after it spreads, cancer becomes much more difficult to treat.

To spread, or “metastasize,” cancer cells must enter the blood stream or lymph system, travel through its channels, and then exit to another area or organ in the body. This final exit is the least understood part of the metastatic process. Previous research has shown cancer cells are capable of producing “invadopodia,” a type of extension that cells use to probe and change their environment. However, their significance in the escape of cancer cells from the bloodstream has been unclear.

In the study, the scientists injected fluorescent cancer cells into the bloodstream of test models, and then captured the fate of these cells using high-resolution time-lapse imaging. Results confirmed the cancer cells formed invadopodia to reach out of the bloodstream and into the tissue of the surrounding organs — they essentially formed “tentacles” that enabled the tumor cell to enter the organ. However, through genetic modification or drug treatment, the scientists were able to block the factors needed for invadopodia to form. This effectively stopped all attempts for the cancer to spread.

The study findings confirm invadopodia play a key role in the spread of cancer. Most importantly, they suggest an important new target for therapy. If a drug can be developed to prevent invadopodia from forming, it could potentially stop the spread of cancer.

“The spread of cancer works a lot like plane travel,” says lead author Dr. Hon Leong, now a Scientist at Lawson Health Research Institute and Western University. “Just as a person boards an airplane and travels to their destination, tumor cells enter the bloodstream and travel to distant organs like the liver, lungs, or brain. The hard part is getting past border control and airport security, or the vessels, when they arrive. We knew that cancer cells were somehow able to get past these barriers and spread into the organs. Now, for the first time, we know how.”

“Metastasis is the deadliest aspect of cancer, responsible for some 90% of cancer deaths,” says Dr. John Lewis, the Frank and Carla Sojonky Chair in Prostate Cancer Research at the University of Alberta. “These new insights give us both a new approach and a clinical window of opportunity to reduce or block the spread of cancer.”

source : http://www.sciencedaily.com/releases/2014/08/140829175428.htm

Knowledge is power: Men who are uneducated about their prostate cancer have difficulty making good treatment choices

UCLA researchers found that men who aren’t well educated about their disease have a much more difficult time making treatment decisions, called decisional conflict, a challenge that could negatively impact the quality of their care and their long-term outcomes.

The study should serve as a wake-up call for physicians, who can use the findings to target men less likely to know a lot about their prostate cancer and educate them prior to their appointments so they’re more comfortable making treatment decisions, said study first author Dr. Alan Kaplan, a resident physician in the UCLA Department of Urology.

“For prostate cancer, there is no one right answer when it comes to treatment. It comes down to the right answer for each specific patient, and that is heavily dependent on their own personal preferences,” Kaplan said. “Men in general, and specifically economically disadvantaged men, have a hard time deciding what their preferences are, how they feel about any possible complications and what the future after treatment might be like. If you don’t know anything about your disease, you’ll have a really tough time making a decision.”

The findings from the one-year study appear in the early online edition of the peer-reviewed journal Cancer.

The research team surveyed 70 men at a Veterans Administration clinic who were newly diagnosed with localized prostate cancer and had enrolled in a randomized trial testing a novel shared decision-making tool. They collected baseline demographic and clinical such as age, race, education, co-existing medical conditions, relationship status, urinary and sexual dysfunction and their prostate cancer knowledge.

UCLA researchers talked one-on-one with the men after they had received their cancer diagnosis, but before they consulted with a physician. Median age of the men in the study was 63 years, 49% were African American and 70% reported an annual income of less than $30,000.

Kaplan said the team found that a low level of prostate cancer knowledge was associated with increased decisional conflict and higher uncertainty about what treatment to choose. Low levels of prostate cancer knowledge also were associated with lower perceived effectiveness — meaning the less they knew about their cancer, the less confidence they had that the treatment would be effective.

“Knowledge about prostate cancer is an identifiable target. Interventions designed to increase a patient’s comprehension of prostate cancer and its treatments may greatly reduce decisional conflict,” Kaplan said, adding that further study is needed to better characterize this relationship and identify effective targeted interventions.

“If you get shot in the gut, there aren’t many options. You go into the operating room to get fixed up,” he said. “With prostate cancer, there are lots of options and not all are right for everybody.”

Men with prostate cancer might need to decide between surgery versus radiation or opting for active surveillance, in which patients are monitored closely for changes in the progression of their cancer and are tested at regular intervals. Prostate cancers can also be treated implantable radioactive seeds or tumors may be burned or frozen as treatment.

Another benefit to reducing decisional conflict is that patients who feel comfortable with their decision may regret their decisions less down the line, Kaplan said. They’re less likely to sue their doctors and generally experience better outcomes.

“In a way, it’s like buying a car. You prepare, you read reports, do your homework,” Kaplan said. “If something goes wrong with the car, you feel OK because you knew what you were getting into. When patients take ownership of the decision-making process, their outcomes are better.”

Kaplan said economically disadvantaged men may be having more difficulty because they may not have as much experience negotiating the healthcare system and are less confident when communicating with doctors.

“Doctors, we know intuitively, should spend more time with their patients, especially when they’re making an important decision,” he said. “But all of us are challenged with the numbers of patients we must see in a day. If you know beforehand that a patient has a poor knowledge about his cancer, that’s someone you need to spend more time with.”

Doctors may also want to provide these patients with educational information before their consultation so they can begin to increase their prostate cancer knowledge, Kaplan said.

Prostate cancer is the most frequently diagnosed cancer in men aside from skin cancer. An estimated 233,000 new cases of prostate cancer will occur in the United States in 2014. Of those, nearly 30,000 men will die.

source : http://www.sciencedaily.com/releases/2014/08/140827090136.htm