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Posts Tagged ‘cancer research

Science Policy Around the Web – April 7, 2017

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By: Kseniya Golovnina, PhD

Cancer Research

RNA-Seq Technology for Oncotargets Discovery

One of the most significant discoveries in cancer research, using the “Big Data” approach with experimental validations, was made recently by Chinese and American scientists together with Splicingcodes.com. They described the first cancer predisposition, familially-inherited, fusion gene, KANSARL, specific to populations with European ancestry, by using advanced RNA-sequencing (RNA-seq) of cancer transcriptomes.

A fusion gene is a hybrid formed from two previously separate genes as a result of chromosomal rearrangements. Often, fusion genes are oncogenes. The first fusion gene abnormality was described in a human malignancy and was called the Philadelphia chromosome. In the early 1980s, scientists showed that a translocation between chromosomes 9 and 22 led to the formation of a fusion gene (BCR/ABL1), which produced a chimeric protein with the capacity to induce chronic myeloid leukemia. KANSARL is the most prevalent cancer gene discovered so far. Scientists systematically analyzed the RNA-seq data of many cancer types from different parts of the world, together with RNA-seq datasets of the 1000 Genome Project. KANSARL fusion transcripts were rarely detected in tumor samples of patients from Asia or Africa, but occurred specifically in 28.9% of the population of European origin.

Scientists from Cancer Genome Anatomy project at the National Cancer Institute (NCI), using sophisticated sequencing techniques, have identified 10,676 gene fusions among cancer-related chromosomal aberrations. Splicingcodes.com has identified over 1.1 million novel fusion transcripts, many of which are likely biomarkers of diseases. Fusion genes play an important role in diagnosis and monitoring of cancer treatment progress by measuring the disappearance of the fusion and, thereby, the disappearance of the tumor tissue. Currently, several clinical trials are aimed at treating fusion-positive patients with a range of targeted therapies, which will hopefully lead to novel therapy development and save patients’ lives. (Splicingcodes)

Biotechnology

Turning Mammalian Cells into Biocomputers to Treat Human Disease

Engineering cells by manipulating DNA and controlling their performance is a growing field of synthetic biology. Scientists have been working with bacterial cells for years to perform different controlled actions, for example, lighting up when oxygen levels drops. Bacterial cells, including Escherichia coli, have a simple genome structure and are relatively easy to manipulate. Using bacterial cells, it was possible also to join several genetic circuits within a single cell to carry out more complex actions.

After successful engineering in bacteria, researchers have aimed to create genetic circuitry to detect and treat human disease in mammalian cells. Most of the attempts have failed due to the complexity of the mammalian genome, until a group of biomedical engineers from Boston and Basel, Switzerland decided to upgrade their DNA “switches”. They used an ability of special enzymes, DNA recombinases, to selectively cut and stitch DNA. The new system in mammalian cells is called ‘Boolean logic and arithmetic through DNA excision’ (BLADE). BLADE founders built a wide variety of circuits (113), each designed to carry out a different logical operation with 96.5% success. This Boolean system has great potential for applications in cell and tissue engineering. One exciting possibility is engineering T-cells with genetic circuits that initiate a suicide response to kill tumors when they detect the presence of two or three “biomarkers” produced by cancer cells. (Robert F. Service, ScienceNews)

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Written by sciencepolicyforall

April 7, 2017 at 9:22 am

Science Policy Around the Web – January 27, 2017

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By: Nivedita Sengupta, PhD

Source: NIH Image Gallery on Flickr, under Creative Commons

Human Research Regulation

US Agency Releases Finalized ‘Common Rule’, Which Govern Human-Subjects Research

On September 8, 2015 the US Department of Health and Human Services (HHS) proposed significant revisions to the Federal Policy for the Protection of Human Subjects which is also known as the “Common Rule”. “Common Rule” is the set of federal regulations governing the conduct of clinical research involving human subjects. Among the proposed changes, an important one was regarding getting peoples’ consent before using the biological samples for subsequent studies. On 18th January 2017, the final version of the rule was released in which the proposed change was abandoned. This is a blow to the patient-privacy advocates, however the US National Academies of Sciences, Engineering and Medicine argued against that requirement and others citing that the changes would impose an undue burden on researchers and recommended that it be withdrawn.

The current version of Common Rule has generated mixed feelings among people. Researchers are happy that the government listened to scientists’ fears about increased research burdens whereas people like Twila Brase, president and co-founder of Citizens’ Council for Health Freedom in St Paul, Minnesota, are disappointed as they believe that these specific changes are ought to be made. Moreover the new version of the Common Rule requires that scientists include a description of the study, along with the risks and benefits, on the consent forms used by patients, and federally-funded trials should post patient consent forms online. However, these requirements do not extend to trials that are conducted with non-federal funds. (Sara Reardon, Nature News)

Biomedical Research

An Open-Science Effort to Replicate Dozens of Cancer-Biology Studies is Off to a Confusing Start

The Reproducibility Project on Cancer Biology was launched in 2013 to scrutinize the findings of 50 cancer papers from high-impact journals. The aim is to determine the fraction of influential cancer biology studies that are sound. In 2012, researchers at the biotechnology firm Amgen performed a similar study and announced that they had failed to replicate 47 of 53 landmark cancer papers but they did not identify the studies involved. In contrast, the reproducibility project makes all its findings open. Full results should appear by the end of the year and eLife is already publishing five fully analyzed reports in January. Out of the five, one failed to replicate and the remaining four showed replication results that are less clear.

These five results paint a muddy picture for people waiting for the outcome to determine the extent of impact of these studies. Though some researchers praised the project, others feared unfair discredit of their work and career. According to Sean Morrison, a senior editor at eLife, the reason for the “uninterpretable” results is “Things went wrong with tests to measure the growth of tumors in the replication attempts and the replication researchers were not allowed to deviate from the protocols, which was agreed at the start of the projects in consultation with the original authors”. “Doing anything else — such as changing the experimental conditions or restarting the work — would have introduced bias”, says Errington, the manager of the reproducibility project.

According to Errington, the clearest finding from this project is that the papers include very few details about their methods. The replication researchers had to spend hours to work out the detailed protocols and reagents along with the original authors. Even after following the exact protocols, the final reports include many reasons why the replication studies might have turned out differently, including variations in laboratory temperatures to tiny variations in how a drug was delivered. He thinks that the project helps to bring out such confusing details to the surface, and it will be a great service for future follow up work to develop a cure for cancer. However, scientists think that such conflicts mean that the replication efforts are not very informative and couldn’t be compared to the original and will only cause delays in advancing future clinical trials. (Monya Baker and Elie Dolgin, Nature News)

 

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Science Policy Around the Web – June 16, 2016

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By: Ian McWilliams, Ph.D.

Kris Krüg via Photo Pin cc

Climate Change

Underground injections turn carbon dioxide to stone

In the race to stop or reverse global warming, scientists in Iceland have discovered a method that could trap the greenhouse gas carbon dioxide (CO2) underground by turning the gas into stone. Researchers found that injecting CO2 into volcanic rock leads to the formation of carbonate minerals. Though the project, termed CarbFix, is still in development it could have important implications for climate change and for incentivizing clean energy policies.

Injecting CO2 underground into sedimentary rock (i.e. sandstone) or depleted oil wells has long been an attractive method of carbon capture and storage  (CCS), but there are concerns that fissures in the rock layers could lead to leakage of CO2 back into the atmosphere. In a joint effort, Icelandic, American, and French scientists proposed that injecting CO2 into layers of basalt could improve this method. Basalt is rock formed by volcanic activity and contains metals such as calcium and magnesium that can react with CO2 to form carbonate minerals, such as calcite, in a process known as carbonation. In this injection process, CO2 is first separated from gaseous emission then dissolved in water to form carbonic acid that is injected into basalt formations 400 to 800 meters below the surface in Iceland. A heavy carbon tracer was included in this mix so that the scientists could track the sequestration of carbon. Over a year and a half after their initial injections, the researchers found that 95% of the injected carbon had been converted to calcite and other minerals, surprising the researchers that carbonation could happen so quickly.

Though these results are promising, many hurdles remain. The carbonation process is resource intensive and requires large amounts of water and electricity, which may limit its environmental impact and commercial scalability. Additionally, while basalt is found around the world and could allow for the indefinite storage of billions of tons of CO2 with minimal leakage risk, introducing large amounts of CO2 into the ground could lead to unforeseen consequences. Although the researchers admit they were surprised by how quickly the CO2 turned to stone in their initial trials, it remains unknown how long the process will take on a commercial scale.

Members of CarbFix admit that the largest obstacle is still a financial one. With no price on carbon emissions, power companies have little to no incentive to pursue this technology. Still, the project has great potential.  Since we depend on fossil fuels and likely will for many more years, “we have to decarbonize our energy infrastructure” according to study author Juerg Matter. Matter further stated that “if it’s mineralized within a human lifetime, then we know we are on a successful pathway”. With improvement, turning CO2 to stone could become a viable strategy for controlling greenhouse gas emissions and curb the deleterious effects of our energy dependence. (Eli Kintisch, Science Magazine)

Cancer Therapeutics

U.S regulator says too many drug makers chasing same cancer strategy

Immunotherapy has revolutionized the field of oncology, but some worry that too many companies are focused on developing therapeutics that target the same pathways. At the American Society of Clinical Oncology’s annual meeting last week, Dr. Richard Pazdur, head of the Food and Drug Administration’s (FDA) Office of Oncology Drug Products commented on the abundance of therapies that disable the protein PD-1, which unleashes the immune response against tumors. So far Merck, Bristol-Myers Squibb, and Roche have all received FDA approval for therapies that target PD-1, and many more drug makers are developing similar strategies. Though these drugs have had remarkable success in the treatment of skin, lung, and bladder cancers, Pazdur encouraged companies to pursue other strategies and to invest in more novel drugs.

Pharmaceutical companies have countered that the future of cancer therapy is combining therapies to target multiple mechanisms of disease simultaneously and that approval for their own PD-1 targeting drug will allow for greater flexibility. Approximately 20 percent of patients treated with PD-1 blockers respond to treatment, with some having long-lasting remissions. However, a recent study demonstrated that combining two different immunotherapy drugs increased survival compared to treatment with either drug alone.  While most of the studies have been done in patients with advanced disease, Pazdur and other experts agree that earlier use could be beneficial for many diseases. Indeed, these treatments are currently being tested in a wide variety of cancers at earlier stages. Furthermore, there are significant costs associated with these therapies with an average price of $150,000 per year. Competition could also help lower the costs, leading to greater benefits for patients. (Deena Beasley, Reuters)

STEM Education

Genuine research keeps students in science

A new study has found that actively involving students in learning rather than in traditional lectures and labs can help lower the attrition rate in STEM fields. In a program at the University of Texas, instructors in the College of Natural Sciences replaced standard introductory courses with a three-course sequence that focuses on problem-solving and hypothesis-driven research. The program, called the Freshman Research Initiative (FRI), was launched in 2005 and has since seen thousands of students complete the program. Participants choose a research stream in which they will experience hands-on learning alongside faculty and graduate students. With numerous research topics that include everything from autonomous robots to genomics to white dwarf stars, students have the opportunity to explore unanswered questions and contribute to larger research projects in faculty-led laboratories.

Researchers have analyzed the results from this initiative and found that, while there was no statistically significant different in grade point average, 94% of FRI students completed a STEM degree compared to 71% of non-FRI students. Students from underrepresented minority groups also achieved high retention and graduation rates through the program, further demonstrating that the initiative could be a successful alternative to traditional internships. These results may provide insight into how to incentivize students to complete their education and could point the way for a cost-effective approach to reach President Obama’s challenge to produce 1 million more STEM-trained workers by 2020. (Jeffrey Mervis, Science Magazine)

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Written by sciencepolicyforall

June 16, 2016 at 11:00 am

Science Policy Around the Web – April 29, 2016

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By: Rebecca Meseroll, Ph.D.

Photo source: pixabay.com

Smoking cessation policy

British medical group recommends switch to e-cigarettes

The Royal College of Physicians (RCP) released a report this week encouraging cigarette smokers to switch to electronic cigarettes (e-cigarettes) as a step toward quitting smoking entirely.  E-cigarettes provide a source of nicotine, the addictive chemical in cigarettes, without tar and other cancer-causing additives.  The report found that the benefits in switching to e-cigarettes far outweigh the risks, noting that smoking is the largest avoidable public health threat in the UK and the health hazards of inhaling vapor from e-cigarettes amounts 5% or less of the risk of smoking cigarettes. These recommendations are somewhat at odds with the stance of public health officials in the US, including the Centers for Disease Control and Prevention, who have been more cautious about e-cigarette use and have focused on potential risks.  Major concerns include the use of e-cigarettes as a gateway to other tobacco products for nonusers, especially youth, and the unknown effects of inhaling additives in the nicotine liquid.  The Food and Drug Administration is has proposed to extend its tobacco authority to e-cigarettes and is currently devising their recommendations for regulation, so the US public policy on e-cigarette use will likely be addressed formally in the near future.  Public health officials on both sides of the Atlantic will no doubt be observing the impact of the RCP’s recommendation on smoking cessation and amending their policies accordingly. (Sabrina Tavernise, The New York Times)

Priorities in health policy

Proliferation of multiple cancer moonshot programs raises some concerns

Several cancer “moonshots”, initiatives aimed at finding a cure for cancer, have been announced in recent months.  Most famous perhaps is the proposed $1 billion effort spearheaded by Vice President Joe Biden, in addition to three other privately-funded initiatives by the Parker Institute, Johns Hopkins University, and the Cancer MoonShot 2020 program.  Some cancer researchers have expressed concern over the proliferation of these different efforts without a strong central leadership, which could lead to unintended overlap of topics and a waste of precious research funds. One issue in coalescing these efforts is that the private enterprises may have different goals from the moonshot proposed by the government, including the need to satisfy investors.  Yet it does not appear that these efforts will be operating completely at cross-purposes, as all three private enterprises will have representation on the government’s advisory panel for Biden’s moonshot, so there will be at least some awareness among the different projects about what the other initiatives are doing.  One advantage of the involvement of privately-funded cancer moonshots is that they can begin work immediately; the government project still remains to be approved and funded by Congress which may balk at the high price tag or be otherwise reluctant to fund a large White House initiative this late in Obama’s presidency. (Erika Check Hayden, Nature)

Global childhood health

Childhood obesity on the rise in rural China

Childhood obesity has been generally on the rise across the globe in the 21st century, and a decades-long study of children in rural Shandong, China found that childhood obesity has absolutely skyrocketed since 1985.  Previous studies have demonstrated the rise in obesity in China, now second in the world behind the US, but the results from the current study on the rural population are staggering.  The rate of overweight and obese boys rose from 0.5% to 30.7% between 1985 and 2014, and for girls from 0.8% to 20.6%.  The authors of the study implicate a shift toward high energy, high fat, low fiber diets coupled with a decrease in physical activity in this astonishing trend.  The rise in obesity also coincides with increasing wealth in rural Chinese households, with previously poor families able to afford more food, so overfeeding during a time of plenty is likely another contribution to the problem.  Public health outcomes of this trend could be very serious; childhood obesity can lead to major deleterious effects, including cardiovascular disease, diabetes, and osteoarthritis.  The authors of the study conclude that rural China should be included in public efforts and education to curb childhood obesity and prevent a generation from suffering the impaired health complications that come with it.

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Written by sciencepolicyforall

April 29, 2016 at 9:00 am