Rice seniors Brian Ho, Rachel Hoffman and Eric Sung have developed a novel way to analyze data for cancer researchers who hope to use magnetic nanoparticles to locate signs of cancer that X-rays would never spot. All magnets (or materials prone to magnetism) have magnetic "moments," like invisible needles that can move and react to magnetic fields, even if their physical hosts can't. These ghostly needles align when exposed to an external magnetic field; when the field is removed, they "relax" once again. Relaxometry measures this latter characteristic. It turns out the moments relax at a very different rate when they belong to nanoparticles that are bound to cancer cells. The students are working with Rice adviser Béatrice Rivière, the Noah G. Harding Chair and a professor of computational and applied mathematics, and doctors at the University of Texas MD Anderson Cancer Center in Houston to develop computer programs that analyze "traces" of these moments as they relax. Albuquerque, N.M.,-based Senior Scientific, in collaboration with MD Anderson, is developing a commercial relaxometry platform for the early detection of cancer. The 25-nanometer superparamagnetic iron-oxide nanoparticles are enhanced with antibody proteins that target biomarker proteins produced by cancer cells, Sung said. "Once they bind to the cells, their range of motion is severely restricted, and this restricted movement is pretty important," he said. "Once you apply an external magnetic field, the particles' dipoles will align to counteract the field. Once the dipoles face each other, then you have a magnetic field of essentially zero. But the interesting part to us is what comes after." The students and the MD Anderson team are working to quantify this relaxation phase because it marks the location of cancer cells in lab samples and in mice. Unbound nanoparticles will randomly reorient themselves in less than a millisecond, but because antibody-associated nanoparticle complexes that are bound to cancer cells are restricted in their movement, their magnetic relaxation is a lot slower – up to a second, Sung said. "We're figuring out exactly what that means." he said. The team noted today's best cancer detection methods only catch tumors with more than 10 million cancer cells. The new approach has the potential to detect tumors with as few as 20,000 cells. The students expect methods that rely on relaxometry will also be safer than current methods that expose patients to ionizing radiation. The students' software addresses two problems that can corrupt relaxometry data. One is that physical motion – like a patient's breathing – can displace the target signal and skew the results. The other is what the students call "flux jumps," a recording artifact that causes a wholesale shift in the data. "The flux jump has to do with the way it's measured," Sung said. "But we've figured out an algorithm to take care of both these things. And it looks pretty nice." Hoffman said the Rice team brought new perspective to the problem recognized by MD Anderson's David Fuentes, an assistant professor in the Department of Imaging Physics, and his colleagues. "They were looking at it very theoretically, whereas we look at it more pragmatically," she said. "We researched what we can do with this particular data, as opposed to trying to develop an algorithm that could be applied to any data set." "Indeed, the senior design team's contribution to motion correction and flux-jump detection will have a lasting impact and will be incorporated into future analysis pipelines," Fuentes said. Ho said the Rice team's next step is to create a way to generate synthetic data traces to test the program. "Once we're able to put in some flux jumps and breathing spikes, we can quantify how good our algorithm is," he said. Explore further: How many nanoparticles heat the tumor?
Welcome to today’s installment of Bioscience Bulletin, where we bring you the most popular headlines from the week. Chronic Stress Causes Brain Inflammation, Memory Loss Researchers from Ohio State University performed experiments on mice that suggest long-term stress can hurt short-term memory. The mice exposed to repeated stress couldn’t remember where the escape hole was in a maze they had previously mastered. The team also observed brain changes in the stressed mice, including inflammation associated with the presence of immune cells, known as macrophages. Herpes, Chlamydia Could Cause Alzheimer’s, Experts Say in Editorial Scientists are calling for more research and funding to look at Alzheimer’s potentially caused by the herpes virus and chlamydia bacteria. Authors of the editorial calling for more research said that it is known that Alzheimer’s disease has a dormant microbial component and that this microbial presence in blood may also play a pivotal role in causing systemic inflammation, characteristic of Alzheimer’s. Diet High in Certain Carbohydrates Could Increase Lung Cancer Risk A new study suggests people should avoid diets filled with foods with a high glycemic index (GI), such as white bread and bagels, because it could put them at a significantly higher risk of developing lung cancer. The team from the University of Texas MD Anderson Cancer Center surveyed 1,905 recently diagnosed lung cancer patients and compared them to 2,413 healthy individuals. They found that those with the highest daily GI had a 49 percent increased risk of lung cancer compared to those with the lowest daily GI. Breast Cancer Drug Combination Could Shrink Tumors in Days A new drug combination of Herceptin (trastuzumab) and lapatinib has had promising results, shrinking or even destroying tumors that are HER-2 positive within just 11 days before surgery. A recent study observed the tumor size in 257 women with breast cancer in the days between diagnosis and when they had their tumor removed. Women received either one drug, both drugs in combination, or no treatment before surgery. About a quarter of the 66 women who received both drugs had tumors that were too small for a second measurement before surgery. GMO Mosquito Gets Finding of 'No Significant Impact' from FDA The genetically engineered Aedes Aegypti male mosquito may be on its way to FDA approval. The mosquito breeds with females and produce offspring that do not live to adulthood. It could be a pway to spread the spread of disease such as Zika, dengue and yellow fever. The FDA announced preliminary findings of no significant impact, the agency said it was “pleased” with.
Precision oncology promises to pair individuals with cancer with drugs that target the specific mutations in their tumour, in the hope of producing long-lasting remission and extending their survival. The basic idea is to use genetic testing to link patients with the drugs that will work best for them, irrespective of the tissue of origin of their tumour. Enthusiasm has been fuelled by reports of exceptional or super responders — individuals for whom experimental therapies seem to work spectacularly well. In one such example, an individual with metastatic bladder cancer showed a dramatic response to the drug everolimus1. Sequencing later revealed that the patient had a mutation that affects the mTOR pathway, which is the mechanism of action of everolimus. Yet despite the hype surrounding rare cases such as these, most people with cancer do not benefit from the precision strategy, nor has this approach been shown to improve outcomes in controlled studies. Precision oncology remains a hypothesis in need of verification. Few patients benefit from precision oncology. Data from some 2,600 people enrolled in a sequencing programme at the MD Anderson Cancer Center in Houston, Texas, showed that just 6.4% were paired with a targeted drug for identified mutations2. Similarly, the Molecular Analysis for Therapy Choice (NCI-MATCH) trial at the US National Cancer Institute has enrolled 795 people who have relapsed solid tumours and lymphoma, but as of May 2016 it had only been able to pair 2% of patients with a targeted therapy3. But being assigned such a therapy is not proof of benefit. When patients with diverse, relapsed cancers are given drugs based on biological markers, only around 30% respond at all, and the median progression-free survival is just 5.7 months4. Multiplying the percentage of patients receiving targeted therapies by this response rate, I estimate that precision oncology will benefit around 1.5% of patients with relapsed and refractory solid tumours. It is on this tiny proportion of patients that the hopes for precision oncology have been built. Although many patients have undergone sequencing in the past decade (Foundation Medicine, a commercial provider of tumour profiling, has sequenced at least 18,000 patients), the number of reported cases of exceptional and super responders over that time are few. In a search of the biomedical literature with a colleague, we identified only 32 cases5. Moreover, even when vignettes such as these are reported, they often have major gaps. The number and duration of responses to previous therapies, and the number of patients who were treated to identify the super responder5, are often omitted. Because even the most serious malignancies, such as pancreatic cancer, exist along a continuum, some patients are already destined to outlive the average. Indeed, we found several cases in which the 'exceptional' responders had already experienced exceptional responses to conventional chemotherapy before their supposedly miraculous response to precision oncology5. It is hard to avoid the unsettling conclusion that such cases do not reflect the success of precision oncology, but rather the selective reporting of individuals who were always likely to do well. When considered objectively, the prospects and potential of precision oncology are sobering. At best, we may expect short-lived responses in a tiny fraction of patients, with the inevitable toxicity of targeted therapies and inflated cost that this approach guarantees. In medical science, the ultimate judge of a therapeutic strategy is the randomized controlled trial. So far, precision oncology has been tested in only one such published study6. The SHIVA trial assigned 99 patients with cancer to therapies based on an identified mutation or mutations, and 96 patients to the treatment selected by their physicians. Median progression-free survival, the primary endpoint, was almost equally poor in both cases (2.3 and 2.0 months, respectively). No single trial can prove that a therapy does not work in any circumstances, and SHIVA is no exception. It paired patients with drugs for 'pathway' mutations, not just for mutations that can be targeted with drugs, allowing those running the trial to enrol more than a quarter of screened patients. But further randomized controlled trials are needed to test alternative hypotheses, and the use of different medications and alternative pathways. These trials will have to balance applicability and generalizability (the percentage of screened patients that can be enrolled) against the strength of the biological rationale. Several more trials are needed before we can judge whether this strategy is viable. Precision oncology is inspirational. What doctor or patient would not want to harness genetics to tailor a therapy to an individual? But travelling back in a time machine is also inspirational. Who would not want to wind back the clock to remove their cancer before it spreads? In both cases, however, as of 2016, the proposal is neither feasible, cost-effective nor assured of future success. Yet in only one of these cases does the rhetoric so far outpace the reality that we risk fooling even ourselves.
News Article | April 6, 2016
Another study has come out adding to the growing body of evidence that associates so called “bad” carbohydrates with increased risks of cancer. The current findings, presented Tuesday at the Experimental Biology 2016 meeting in San Diego, suggest that reducing the amount of sugary beverages and processed lunch foods consumed can decrease the risk for prostate and breast cancers. Researchers, led by Nour Makarem, a Ph.D. student at New York University, analyzed health records of 3,100 volunteers whose diets were tracked through detailed food frequency questionnaires beginning in 1991. Participants’ intake of certain foods were categorized by glycemic index (GI), which is a measure of the quality of dietary carbohydrates based on the impact on blood sugar levels, and glycemic load, which measures most the quantity and quality of carbs in a particular food item. Then the team analyzed the food intake in relation to participants’ cancer rates. Regular consumption of processed foods such as pizza, burgers and lunch meat doubled the risk of developing prostate cancer, while high intake of sugary beverages, such as soft drinks and fruit juices, was associated with a three times greater risk of prostate cancer. Researchers found that eating foods with a high glycemic load was associated with an 88 percent increased risk of prostate cancer, after accounting for multiple cancer risk factors. In contrast, consuming healthy carbohydrates with a low glycemic index, such as legumes, non-starchy vegetables and whole grains seemed to have a protective effect, and was associated with 67 percent lower breast cancer risk. “One of the most important findings here is that the type of carbohydrate-containing foods you consume can impact your cancer risk,” lead study author Makarem said in a prepared statement. “It appears that healthy carbohydrate sources, such as legumes, tend to protect us from cancer, but non-healthy ones, such as fast foods and sugary beverages, seem to increase the risk of these cancers.” Interestingly, those with the highest level of carbohydrate intake also had the highest consumption of fruits, vegetables, whole grains and legumes. This suggests it’s the quality, not the quantity of carbohydrates that matter. A sentiment echoed in a separate study from the University of Texas MD Anderson Cancer Center that found eating foods high in GI, such as white bread, bagels or cornflakes, was associated with a significantly higher risk of developing lung cancer. Read more on that story here. Individually, Makarem’s study linked, legumes, including beans, lentils and peas, to a 32 percent lower risk of obesity-related cancers such as breast, prostate and colorectal cancer. One limitation of the study is that 99 percent of the participants were Caucasian. More research is needed on ethnically-diverse cohorts to see if the associations hold true, the researchers said. Establish your company as a technology leader! For more than 50 years, the R&D 100 Awards have showcased new products of technological significance. You can join this exclusive community! Learn more.
News Article | April 13, 2016
Sean Parker is deathly allergic to peanuts. If he accidentally eats a rogue nut and doesn't receive an epinephrine injection, he will stop breathing. Parker's struggle with life-threatening allergies hasn't stopped him from achieving fortune (as the first investor in Facebook), fame (Justin Timberlake played him as a charismatic hustler in the film The Social Network), and a track record for changing entire industries (remember Napster?). It did, however, inspire him to spend countless hours in an Internet rabbit hole researching the mysteries of the human immune response. "I'm totally fascinated by the immune system," he told me by phone this week, while trying to escape the New York rain. "Like my interest in other scientific fields, I took a deeper dive and got more and more invested." In December 2014, he got his feet wet by making a $24 million donation to the Stanford University School of Medicine, which is earmarked for allergy research. Today, he is announcing the $250 million-funded Parker Institute, a research effort to develop targeted therapies to treat cancer, which is noteworthy in its ability to evade the immune system. That's the single largest financial contribution to the field of immunotherapy ever. It's also Parker's most ambitious effort in biotech. To discover breakthrough therapies, Parker has personally helped recruit a brain trust of more than 40 laboratories and 300 researchers from the top cancer centers, including MD Anderson, Memorial Sloan Kettering, Penn Medicine, Stanford, and the University of California, San Francisco (UCSF). Strategic advisers include Jeff Huber, a longtime Googler who is now working to develop a blood test for cancer detection, and executives from a variety of pharma companies including Amgen and Merck. Dr. Jeff Bluestone, a well-known researcher and a former provost at UCSF, is leading the initiative as its chief executive offer. "I've been following the explosion of cancer immunotherapies in the past five years," Bluestone says. "I met Sean a few times, and he asked if I'd join." Parker seems confident he can create momentum outside the ivory towers of medical research, even though $250 million is a drop in the bucket compared to the costs of drug development, which is typically in the billions. The Parker Institute is hoping that its partners, the pharmaceutical companies, will fund the early clinical trials and shoulder the costs of bringing a new therapy to market. "From my perspective as an entrepreneur, I know we can see results faster," he says. He's identified two major flaws with research today: The lack of collaboration between researchers, and the frequent intellectual property disputes over new technologies. As a condition of partnering with the Parker Institute, researchers are expected to work with each other instead of pursuing personal glory. They must also agree to license any new technology they develop through the institute. After watching scientists behind one of most important biotech breakthroughs in recent history, a gene-editing technology known as CRISPR, get embroiled in a messy legal battle over patents, Parker is desperate to avoid a scenario in which technologies sit on the shelf for decades while researchers duke it out in court. "I joke around that if you were to roll back the clock and design an industry or field that would produce a breakthrough technology for treating patients and curing disease, this is the last structure you would come up with," Parker adds. In 2011, Parker's good friend, the legendary film producer Laura Ziskin, passed away from breast cancer. The two had frequently discussed the potential of immunotherapy, which was also a subject close to Ziskin's heart. After she died, Parker set about quietly deploying capital into immunotherapy. "I set up a dream team in the scientific establishment, which hadn't embraced the idea yet," he says. But the field quickly entered into a kind of renaissance. Today, immunotherapy is central to the Obama Administration's "moonshot" to cure cancer. Vice President Joe Biden recently predicted that immunotherapy will progress cancer research more in the next 10 years than it has in the past 50. Broadly speaking, cancer immunotherapy researchers seek to understand the mechanisms by which cancer cells evade detection. They are bringing new therapies to market, notably immune checkpoint inhibitors, which help the immune system recognize and target cancer cells as foreign. These therapies are more specific than chemotherapy, which causes damage to many healthy cells. "The way I describe it to my patients is to think about the last time they had a bacterial infection and got really sick," says Dr. Dale Shepard, a medical oncologist at the Cleveland Clinic. "That's an example of a robust immune response." By contrast, some of Shepard's patients have advanced cancers that present with few symptoms. "I see patients all the time that have five-inch tumors that are totally ignored by the immune system." Oncologists like Shepard are cautiously optimistic about the prospects of cancer immunotherapy, as they've seen it work firsthand. Some of the newest treatments, which have been most effective at treating kidney, colon, prostate, and lung cancers, have brought some of Shepard's patients with advanced tumors back from the brink of death. The therapies have even proved tolerable to nonagenarians, like former president Jimmy Carter. But for some patients, such as those with slower-growing cancers, the response has been minimal at best. That said, cancer immunotherapy is not quite a home run yet. The next step for researchers is to better understand why some patients aren't receptive to immunotherapies at all, while others show near-miraculous improvement. Oncologists are also hoping to see new therapies for hematologic cancers, like leukemias and lymphomas. Some 1,500 cancer immunotherapy drugs are currently in the research and development pipeline. Bluestone, who is heading up the Parker Initiative, has already scoped out some near-term research initiatives for the coming year, such as new ways to modify T-cells (the immune system's anti-cancer warriors) to better recognize and kill cancer cells. Additionally, the initiative will provide sophisticated technology to labs such as machines for DNA sequencing. And Bluestone is researching how to apply medical imaging technology, which can offer a three-dimensional picture of tissues and tumors to better understand how these cells communicate with each other. "We want to look deeper than ever before," he says. "We want to identify what cancers come back, and seek out subtle changes in the immune system that we can exploit." Dr. Prateek Mendiratta is a clinical associate of medicine at Duke Cancer Center. He treats patients with cancer every day, and is keeping a watchful eye on developments in the field of immunotherapy. I ask Mendiratta for his thoughts on Sean Parker making a big impact in the space. "Oh wow," he said, seemingly puzzled that a household-name tech billionaire would want to plant a flag in this particular area of research. But on further reflection, Mendiratta came around to the idea of Silicon Valley types investing their time and resources into the space. "We have to keep thinking outside the box," he says. "If more patients can see durable responses and remissions, I'm excited to see people outside of the industry step in." The oncologists I spoke to recognized that physicians desperately need a new set of tools to treat patients. And if an outsider from the tech industry can do it, all power to them. For his part, Parker asks every researcher who wants to get involved about the projects they wish they were doing (a very Silicon Valley question). He says he wants to fund the ideas that have been deemed "too complicated or too ambitious" for the status quo. Shepard is ready for this kind of thinking. "It's a daily frustration for me that traditional chemotherapies don't work as well as we'd like," he says. "I think enough people are willing now to stand up and do the right thing for patients, even if that means changing the way we do things."