Researchers at the University of Southampton have engineered cells with a ‘built-in genetic circuit’ that produces a molecule that inhibits the ability of tumours to survive and grow in their low oxygen environment.
The genetic circuit produces the machinery necessary for the production of a compound that inhibits a protein which has a significant and critical role in the growth and survival of cancer cells. This results in the cancer cells being unable to survive in the low oxygen, low nutrient tumour micro-environment.
As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels. This results in cancer cells needing to adapt to low oxygen environment.
To enable them to survive, adapt and grow in the low-oxygen or ‘hypoxic’ environments, tumours contain increased levels of a protein called Hypoxia-inducible factor 1 (HIF-1). HIF-1 senses reduced oxygen levels and triggers many changes in cellular function, including a changed metabolism and sending signals for the formation of new blood vessels. It is thought that tumours primarily hijack the function of this protein (HIF-1) to survival and grow.
Professor Ali Tavassoli, who led the study with colleague Dr. Ishna Mistry, explains: “In an effort to better understand the role of HIF-1 in cancer, and to demonstrate the potential for inhibiting this protein in cancer therapy, we engineered a human cell line with an additional genetic circuit that produces the HIF-1 inhibiting molecule when placed in a hypoxic environment.
“We’ve been able to show that the engineered cells produce the HIF-1 inhibitor, and this molecule goes on to inhibit HIF-1 function in cells, limiting the ability of these cells to survive and grow in a nutrient-limited environment as expected.
“In a wider sense, we have given these engineered cells the ability to fight back – to stop a key protein from functioning in cancer cells. This opens up the possibility for the production and use of sentinel circuits, which produce other bioactive compounds in response to environmental or cellular changes, to target a range of diseases including cancer.”
The genetic circuit is incorporated onto the chromosome of a human cell line, which encodes the protein machinery required for the production of their cyclic peptide HIF-1 inhibitor. The production of the HIF-1 inhibitor occurs in response to hypoxia in these cells. The research team demonstrated that even when produced directly in cells, this molecule still prevents the HIF-1 signalling and the associated adaptation to hypoxia in these cells.
The next step for the researchers is to demonstrate the viability of this approach to the production and delivery of an anticancer molecule in a whole tumour model system.
Professor Tavassoli adds: “The main application for this work is that it eliminates the need for the synthesis of our inhibitor, so that biologists conducting research into HIF function can easily access our molecule and hopefully discover more about the role of HIF-1 in cancer. This will also let us understand whether inhibiting HIF-1 function alone is enough to block cancer growth in relevant models. Another interesting aspect to the work is that it demonstrates the possibility of adding new machinery to human cells to enable them to make therapeutic agents in response to disease signals.”
A team of University of Pittsburgh researchers has uncovered new details about the biology of telomeres, “caps” of DNA that protect the tips of chromosomes and play key roles in a number of health conditions, including cancer, inflammation and aging.
The new findings were published today in the journal Nature Structural and Molecular Biology.
Telomeres, composed of repeated sequences of DNA, are shortened every time a cell divides and therefore become smaller as a person ages. When they become too short, telomeres send a signal to the cell to stop dividing permanently, which impairs the ability of tissues to regenerate and contributes to many aging-related diseases, explained lead study author Patricia Opresko, Ph.D., associate professor of Environmental and Occupational Health at Pitt, and member of the University of Pittsburgh Cancer Institute Molecular and Cellular Cancer Biology program and Carnegie Mellon University Center for Nucleic Acids Science and Technology.
In contrast, in most cancer cells, levels of the enzyme telomerase, which lengthens telomeres, are elevated, allowing them to divide indefinitely.
“The new information will be useful in designing new therapies to preserve telomeres in healthy cells and ultimately help combat the effects of inflammation and aging. On the flip side, we hope to develop mechanisms to selectively deplete telomeres in cancer cells to stop them from dividing,” said Dr. Opresko.
A number of studies have shown that oxidative stress—a condition where damaging molecules known as free radicals build up inside cell—accelerates telomere shortening. Free radicals can damage not only the DNA that make up telomeres, but also the DNA building blocks used to extend them.
Oxidative stress is known to play a role in many health conditions, including inflammation and cancer. Damage from free radicals, which can be generated by inflammation in the body as well as environmental factors, is thought to build up throughout the aging process.
The goal of the new study was to determine what happens to telomeres when they are damaged by oxidative stress. The researchers suspected that oxidative damage would render telomerase unable to do its job.
“Much to our surprise, telomerase could lengthen telomeres with oxidative damage,” Dr. Opresko said. “In fact, the damage seems to promote telomere lengthening.”
Next, the team looked to see what would happen if the building blocks used to make up telomeres were instead subjected to oxidative damage. They found that telomerase was able to add a damaged DNA precursor molecule to the end of the telomere, but was then unable to add additional DNA molecules.
The new results suggest that the mechanism by which oxidative stress accelerates telomere shortening is by damaging the DNA precursor molecules, not the telomere itself. “We also found that oxidation of the DNA building blocks is a new way to inhibit telomerase activity, which is important because it could potentially be used to treat cancer.”
Dr. Opresko and her team are now beginning to further explore the consequences of oxidative stress on telomeres, using a novel photosensitizer, developed by Marcel Bruchez at Carnegie Mellon University that produces oxidative damage selectively in telomeres. “Using this exciting new technology, we’ll be able to learn a lot about what happens to telomeres when they are damaged, and how that damage is processed,” she said.
Cancer is a notoriously difficult disease to treat. Not only do a wide variety of cancers exist, requiring specialized treatments for each type, but cancer cells within an individual can morph and render previously potent therapeutics ineffective. Thus, there is a continual need to discover new, effective drugs. Research from Dr. Norihiko Nakazawa in the G0 Cell Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) led by Prof. Mitsuhiro Yanagida, may help make the discovery process easier. This research was published in Genes to Cells.
Cancer cells differ from normal cells in a variety of different ways. Most notably, malignant cells exhibit a much higher rate of replication and proliferation than normal ones. The rapid growth of these cells can result in tumor formation and metastasis, or the spreading of cancer to other parts of the body. Fortunately, scientists have been able to exploit these properties to create new treatments. Since the proteins involved in DNA replication are considerably more active in cancer cells than in normal ones, researchers have discovered that drugs which target these proteins will disproportionately affect the malignant cells. These drugs are designed to only affect active proteins, so that even though the same proteins exist in normal cells, the majority of the normal cells will contain inactive proteins at the time of treatment, and thus be unaffected.
Dr. Nakazawa’s research centered on the use of a specific anti-cancer drug, ICRF-193, which targets a protein called DNA topoisomerase II. As part of his research, Dr. Nakazawa treated fission yeast with ICRF-193 and observed the effects. Typically, during cell reproduction, DNA is copied so that a cell temporarily contains twice the amount of DNA than it normally does. These two copies of chromosomal DNA are pulled to different ends of the cell by a protein structure called the mitotic spindle. Once the chromosomal DNA is separated, the cell begins to divide into two identical daughter cells.
When Dr. Nakazawa treated fission yeast with ICRF-193, he noticed that the cells appeared to have difficulty separating after DNA replication had occurred. Instead of separating normally, the mitotic spindle appeared to continue to lengthen despite failing to fully separate the two copies of DNA, producing an arched shape until eventually snapping in the middle. This “arched and snapped” appearance seemed to be unique to the ICRF-193 treated cells.
Researchers can utilize this “arched and snapped” appearance to look for other drugs that affect fission yeast proteins in the same manner. The replication machinery and DNA-bound proteins of fission yeast are highly conserved and thus remarkably similar to other organisms, including humans. Because of this similarity, drugs that affect these proteins in fission yeast are likely to affect the related highly active proteins in human cancers. This research makes it plausible to use fission yeast in the place of human cells in the discovery process of novel cancer drugs.
There are many disadvantages to using human cells in the initial stages of creating a new therapy. Scientists often have to test a large number of compounds in order to find one that is effective against a particular target. Human cells are costly to take care of and require a lot of time and specific conditions in order to grow. According to Dr. Nakazawa, “fission yeast is a relatively fast, easy to use model system that is low cost,” making it advantageous for use in drug screens. Time and cost are often major hurdles in the process of drug development, so any discoveries that expedite the process can help get the next cancer cure in the hands of patients sooner.
A new compound, discovered jointly by international pharmaceutical company Servier, headquartered in France, and Vernalis (R&D), a company based in the UK, has been shown by researchers at the Walter and Eliza Hall Institute and Servier to block a protein that is essential for the sustained growth of up to a quarter of all cancers.
The research presents a new way to efficiently kill these cancerous cells and holds promise for the treatment of blood cancers such as acute myeloid leukaemia,lymphoma and multiple myeloma, as well as solid cancers such as melanoma and cancers of the lung and breast. It is published online today in the journal Nature.
The Servier compound – S63845 – targets a protein of the BCL2 family, called MCL1, which is essential for the sustained survival of these cancer cells.
Institute scientist Associate Professor Guillaume Lessene, who led the Walter and Eliza Hall Institute’s research team in Melbourne, Australia, said the work provided the first clear preclinical evidence that inhibiting MCL1 was effective in targeting several cancer types.
“MCL1 is important for many cancers because it is a pro-survival protein that allows the cancerous cells to evade the process of programmed cell death that normally removes cancer cells from the body,” Associate Professor Lessene said. “Extensive studies performed in a variety of cancer models have shown that S63845 potently targets cancer cells dependent on MCL1 for their survival.”
The institute team of Associate Professor Lessene worked with haematologist Associate Professor Andrew Wei and Dr Donia Moujalled from The Alfred Hospital and Servier scientists, to demonstrate that not only was S63845 effective against several cancer types, but that it could also be delivered at doses that were well tolerated by normal cells.
Dr Olivier Geneste, Director of Oncology Research at Servier, said this preclinical research represented major findings regarding the druggability of MCL1, a valuable and highly challenging target. “S63845 was discovered through collaboration with the fragment and structure based discovery expertise at Vernalis,” he said. “As part of the ongoing Servier / Novartis collaboration on this target class, clinical development of a MCL1 inhibitor should be launched in the near future.”
Associate Professor Lessene said the research provided further evidence of the usefulness of a new class of anti-cancer drugs called BH3 mimetics. “BH3 mimetics inhibit a group of proteins known as the ‘pro-survival BCL-2 proteins’,” he said. “MCL1 is a member of this protein family, and inhibiting it activates the process of programmed cell death. Walter and Eliza Hall Institute researchers revealed the role of BCL-2 in cancer more than 28 years ago and the essential role of MCL1 for the survival of malignant cells four years ago.”
Washington State University researchers have developed a low-cost, portable laboratory on a smartphone that can analyze several samples at once to catch a cancer biomarker, producing lab quality results.
The research team, led by Lei Li, assistant professor in the School of Mechanical and Materials Engineering, recently published the work in the journal Biosensors and Bioelectronics (http://www.sciencedirect.com/science/article/pii/S0956566316308983).
At a time when patients and medical professionals expect always faster results, researchers are trying to translate biodetection technologies used in laboratories to the field and clinic, so patients can get nearly instant diagnoses in a physician’s office, an ambulance or the emergency room.
The WSU research team created an eight channel smartphone spectrometer that can detect human interleukin-6 (IL-6), a known biomarker for lung, prostate, liver, breast and epithelial cancers. A spectrometer analyzes the amount and type of chemicals in a sample by measuring the light spectrum.
Although smartphone spectrometers exist, they only monitor or measure a single sample at a time, making them inefficient for real world applications. Li’s multichannel spectrometer can measure up to eight different samples at once using a common test called ELISA, or colorimetric test enzyme-linked immunosorbent assay, that identifies antibodies and color change as disease markers.
Although Li’s group has only used the smartphone spectrometer with standard lab-controlled samples, their device has been up to 99 percent accurate. The researchers are now applying their portable spectrometer in real world situations.
“With our eight channel spectrometer, we can put eight different samples to do the same test, or one sample in eight different wells to do eight different tests. This increases our device’s efficiency,” said Li, who has filed a provisional patent for the work.
“The spectrometer would be especially useful in clinics and hospitals that have a large number of samples without on-site labs, or for doctors who practice abroad or in remote areas,” he said. “They can’t carry a whole lab with them. They need a portable and efficient device.”
Li’s design works with an iPhone 5. He is creating an adjustable design that will be compatible with any smartphone.
Pioneering researcher cautions doctors against assuming they’re signs of cancer
The human genome is far more complex than thought, with genes functioning in an unexpected fashion that scientists have wrongly assumed must indicate cancer, research from the University of Virginia School of Medicine indicates.
Hui Li, PhD, of the Department of Pathology and the UVA Cancer Center, is a pioneer in a small but emerging field that is challenging fundamental assumptions about human genetics. He seeks to understand what is called chimeric RNA – genetic material that results when genes on two different chromosomes produce “fusion” RNA in a way scientists say shouldn’t happen. Researchers have traditionally assumed these chimeric RNA are signs of cancer, of something gone wrong in the genetic transcription process. But Li’s work shows that’s not always the case. Instead, these strange fusions can also be a normal, functional part of our genetic programming.
“This is actually a double-edged sword for cancer diagnosis and treatment. … It basically says the old practice of finding any fusion RNA and claiming it’s a cancer fusion is over. We can’t just say, OK, we found a fusion, it must be a cancer marker, let’s translate it into a biomarker [to detect cancer],” Li said. “That’s actually dangerous. Because a lot of normal physiology also has fusion RNAs. There’s another layer of complexity.”
Because of Li’s pioneering work, the scientific journal Trends in Cancer invited him to provide an opinion piece outlining the state of his field’s research and the challenges and opportunities that lie ahead. In the new article, he seeks to increase scientists’ awareness of this important nuance in our genetic understanding, and he cautions them that failure to consider the role of normal chimeras could lead to conclusions that are inaccurate, incomplete or flat-out wrong.
“This is the main concept we want to let the field of cancer biology know: This kind of thing exists in normal physiology. It’s not cancer specific,” Li said. “There’s a danger to assuming everything is cancer. That’s actually dangerous. Don’t rush to judgment about all of these chimera you find in cancer cells, because they could occur in normal cells.”
Getting that message out, he said, is important because existing beliefs are so entrenched. “Traditionally, there have been all these assumptions coming back to the central dogma that genetic information is passed from DNA to RNA to proteins. Because the gene is defined as the molecular unit of hereditary information, people don’t assume the units or their RNA and protein products can mix with each other,” he said, noting that even he was skeptical initially. “It was hard for us to believe at first. We were surprised to see such a thing could occur in normal physiology, and it could occur at such a high frequency.”
Better ways to battle cancer
Because these natural chimeras were discovered so recently, relatively little is known about them. Li and his fellow researchers have shown that they occur when the instructions in our DNA are being carried out by RNA inside our cells. But the scientists can’t say how the fusions occur or why they occur or exactly how frequently they occur. And that speaks to how much there is to learn, Li noted. That knowledge will help us to better understand the human genome and to create better ways to detect – and hopefully defeat – cancer. “This opens a window for us to discover new biomarkers and new therapeutic targets, because there’s this whole other layer of complexity,” he said.
To build a foundation for discovery, Li is creating a database of naturally occurring fusions, to help sort normal chimeras from ones that might be signs of cancer. He doesn’t believe that any of the biomarkers now being used for cancer detection are problematic, but the database should accelerate the identification of new biomarkers by saving scientists from having to investigate each chimera individually.
UBC researchers have discovered how cancer cells become invisible to the body’s immune system, a crucial step that allows tumours to metastasize and spread throughout the body.
“The immune system is efficient at identifying and halting the emergence and spread of primary tumours but when metastatic tumours appear, the immune system is no longer able to recognize the cancer cells and stop them,” said Wilfred Jefferies, senior author of the study working in the Michael Smith Laboratories and a professor of Medical Genetics and Microbiology and Immunology at UBC.
“We discovered a new mechanism that explains how metastatic tumours can outsmart the immune system and we have begun to reverse this process so tumours are revealed to the immune system once again.”
Cancer cells genetically change and evolve over time. Researchers discovered that as they evolve, they may lose the ability to create a protein known as interleukein-33, or IL-33. When IL-33 disappears in the tumour, the body’s immune system has no way of recognizing the cancer cells and they can begin to spread, or metastasize.
The researchers found that the loss of IL-33 occurs in epithelial carcinomas, meaning cancers that begin in tissues that line the surfaces of organs. These cancers include prostate, kidney breast, lung, uterine, cervical, pancreatic, skin and many others.
Working in collaboration with researchers at the Vancouver Prostate Centre, and studying several hundred patients, they found that patients with prostate or renal (kidney) cancers whose tumours have lost IL-33, had more rapid recurrence of their cancer over a five-year period. They will now begin studying whether testing for IL-33 is an effective way to monitor the progression of certain cancers.
“IL-33 could be among the first immune biomarkers for prostate cancer and, in the near future, we are planning to examine this in a larger sample size of patients,” said Iryna Saranchova, a PhD student in the department of microbiology and immunology and first author on the study.
Researchers have long tried to use the body’s own immune system to fight cancer but only in the last few years have they identified treatments that show potential.
In this study Saranchova, Jefferies and their colleagues at the Michael Smith Laboratories, found that putting IL-33 back into metastatic cancers helped revive the immune system’s ability to recognize tumours. Further research will examine whether this could be an effective cancer treatment in humans.
Researchers have created a new drug delivery system that could improve the effectiveness of an emerging concept in cancer treatment – to dramatically slow and control tumors on a long-term, sustained basis, not necessarily aiming for their complete elimination.
The approach, called a “metronomic dosage regimen,” uses significantly lower doses of chemotherapeutic drugs but at more frequent time intervals. This would have multiple goals of killing cancer cells, creating a hostile biological environment for their growth, reducing toxicity from the drug regimen and avoiding the development of resistance to the cancer drugs being used.
A system just published in Chemistry of Materials by a group of researchers from Oregon and the United Kingdom offers an even more effective way to deliver such drugs and may be able to greatly improve this approach, scientists say. Further testing is needed in both animals and humans for safety and efficacy.
“This new system takes some existing cancer therapy drugs for ovarian cancer, delivers both of them at the same time and allows them to work synergistically,” said Adam Alani, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the new study.
“Imagine if we could manage cancer on a long-term basis as a chronic condition, like we now do high blood pressure or diabetes. This could be a huge leap forward.”
This approach is still in trial stages, Alani said, but shows promise. In some prior work with related systems in animal tests, OSU and collaborating researchers have been able to completely eradicate tumors.
Total remission, Alani said, may be possible with metronomic dosage, but the initial goal is not only to kill cancer cells but to create an environment in which it’s very difficult for them to grow, largely by cutting off the large blood supply these types of cells often need.
Most conventional cancer chemotherapy is based on the use of “maximum tolerable doses” of a drug, in an attempt to completely eliminate cancer or tumors. In some cases such as ovarian cancer, however, drug-free intervals are needed to allow patient recovery from side effects, during which tumors can sometimes begin to grow again or develop resistance to the drugs being used.
The types of cancers this approach may best lend itself to are those that are quite complex and difficult to treat with conventional regimens based on “maximum tolerable dose.” This includes ovarian, sarcoma, breast, prostate, and lung cancers.
One example of the new metronomic regimen, in this instance, is use of two drugs already common in ovarian cancer treatment – paclitaxel and rapamycin – but at levels a tenth to a third of the maximum tolerable dose. One drug attacks cancer cells; the other inhibits cancer cell formation and the growth of blood vessels at tumor sites.
The new system developed in this research takes the process a step further. It attaches these drugs to polymer nanoparticles that migrate specifically into cancer cells and are designed to release the drugs at a particular level of acidity that is common to those cells. The low doses, careful targeting of the drugs and their ability to work in synergy at the same time appeared to greatly increase their effectiveness, while almost completely eliminating toxicity.
“Our goal is to significantly reduce tumors, slow or stop their regrowth, and allow a person’s body and immune system time to recover its health and natural abilities to fight cancer,” Alani said. “I’m very optimistic this is possible, and that it could provide an entirely new approach to cancer treatment.”
Researchers at The University of Manchester have unlocked the potential of a new test which could revolutionise the way doctors diagnose and monitor a common childhood Leukaemia.
Dr Suzanne Johnson says that cancerous acute lymphoblastic leukaemia cells produce and release special structures that can be traced in the blood.
The discovery could have major implications on the diagnosis, monitoring, drug delivery and treatment of childhood leukaemia.
Dr Johnson publishes the research, which was led by Professor of Paediatric Oncology Vaskar Saha, in the leading journal Blood. This research received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration (Grant agreement no. 278514 – IntReALL); a program grant fromCancer Research UK; and a Bloodwise project grant. Professor Saha is the recipient of an India Alliance Margdarshi Fellowship
Until recently, the ‘Extracellular Vesicles’, as they are known, were thought to be worthless debris. Dr Johnson investigated their presence in the plasma from bone marrow biopsies and discovered their ability to circulate in the blood using mice.
Though there is an 85 to 90% success rate in treatment, children must endure repeat bone marrow biopsies to assess the progress of treatment.
But the researchers hope this discovery might reduce the frequency of the painful procedures, which can also cause bruising, bleeding and infection.
Vesicles, which contain the protein actin and have identifiable characteristics of their parent cell, are typified by branching structures beautifully shown in images produced by the team.
Our research has shown that cancerous Leukaemia cells have the ability to package parts of themselves and then send these structure – vesicles – to anywhere in the body though the blood. That opens up a world of possibilities in terms of monitoring the progress of the disease and making diagnosis quickly and efficiently
Dr Suzanne Johnson
Dr Johnson said: “Our discovery of Extracellular Vesicles could be a game changer in terms of the way we care for children with lymphoblastic leukaemia.
“Our research has shown that cancerous Leukaemia cells have the ability to package parts of themselves and then send these structure – vesicles – to anywhere in the body though the blood.
“That opens up a world of possibilities in terms of monitoring the progress of the disease and making diagnosis quickly and efficiently. They are also internalised by other cells and act as an effective route for cell communication.
“Now the challenge is to investigate whether other cancers produce and release these structures as well.”
Further down the road, the discovery could have implications on the way drugs are delivered to patients, explains to Dr Johnson, if we can find a way to combine them with the vesicles.
And the team also hope that the vesicles might provide individualised information about the tumours, eventually helping doctors to deliver personalised care.
She added: “What is amazing is that Vesicles were previously dismissed as mere debris from the cancerous cell, but we now realise this absolutely not the case. They are far more interesting than that!”
IBM scientists have developed a new lab-on-a-chip technology that can, for the first time, separate biological particles at the nanoscale and could enable physicians to detect diseases such as cancer before symptoms appear.
As reported today in the journal Nature Nanotechnology, the IBM team’s results show size-based separation of bioparticles down to 20 nanometers (nm) in diameter, a scale that gives access to important particles such as DNA, viruses and exosomes. Once separated, these particles can potentially be analyzed by physicians to reveal signs of disease even before patients experience any physical symptoms and when the outcome from treatment is most positive. Until now, the smallest bioparticle that could be separated by size with on-chip technologies was about 50 times or larger, for example, separation of circulating tumor cells from other biological components.
IBM is collaborating with a team from the Icahn School of Medicine at Mount Sinai to continue development of this lab-on-a-chip technology and plans to test it on prostate cancer, the most common cancer in men in the U.S.
In the era of precision medicine, exosomes are increasingly being viewed as useful biomarkers for the diagnosis and prognosis of malignant tumors. Exosomes are released in easily accessible bodily fluids such as blood, saliva or urine. They represent a precious biomedical tool as they can be used in the context of less invasive liquid biopsies to reveal the origin and nature of a cancer.
The IBM team targeted exosomes with their device as existing technologies face challenges for separating and purifying exosomes in liquid biopsies. Exosomes range in size from 20-140nm and contain information about the health of the originating cell that they are shed from. A determination of the size, surface proteins and nucleic acid cargo carried by exosomes can give essential information about the presence and state of developing cancer and other diseases.
exosomes of size 100 nm and larger could be separated from smaller exosomes, and that separation can take place in spite of diffusion, a hallmark of particle dynamics at these small scales. With Mt. Sinai, the team plans to confirm their device is able to pick up exosomes with cancer-specific biomarkers from patient liquid biopsies.
“The ability to sort and enrich biomarkers at the nanoscale in chip-based technologies opens the door to understanding diseases such as cancer as well as viruses like the flu or Zika,” said Gustavo Stolovitzky, Program Director of Translational Systems Biology and Nanobiotechnology at IBM Research. “Our lab-on-a-chip device could offer a simple, noninvasive and affordable option to potentially detect and monitor a disease even at its earliest stages, long before physical symptoms manifest. This extra amount of time allows physicians to make more informed decisions and when the prognosis for treatment options is most positive.”
Report calls for more integration of physical, life sciences for needed advances in biomedical research.
What if lost limbs could be regrown? Cancers detected early with blood or urine tests, instead of invasive biopsies? Drugs delivered via nanoparticles to specific tissues or even cells, minimizing unwanted side effects? While such breakthroughs may sound futuristic, scientists are already exploring these and other promising techniques.
But the realization of these transformative advances is not guaranteed. The key to bringing them to fruition, a landmark new report argues, will be strategic and sustained support for “convergence”: the merging of approaches and insights from historically distinct disciplines such as engineering, physics, computer science, chemistry, mathematics, and the life sciences.
The report, “Convergence: The Future of Health,” was co-chaired by Tyler Jacks, the David H. Koch Professor of Biology and director of MIT’s Koch Institute for Integrative Cancer Research; Susan Hockfield, noted neuroscientist and president emerita of MIT; and Phillip Sharp, Institute Professor at MIT and Nobel laureate, and will be presented at the National Academies of Sciences, Engineering, and Medicine in Washington on June 24.
The report draws on insights from several dozen expert participants at two workshops, as well as input from scientists and researchers across academia, industry, and government. Their efforts have produced a wide range of recommendations for advancing convergence research, but the report emphasizes one critical barrier above all: the shortage of federal funding for convergence fields.
“Convergence science has advanced across many fronts, from nanotechnology to regenerative tissue,” says Sharp. “Although the promise has been recognized, the funding allocated for convergence research in biomedical science is small and needs to be expanded. In fact, there is no federal agency with the responsibility to fund convergence in biomedical research.”
Radiation therapy not only kills cancer cells, but also helps to activate the immune system against their future proliferation. However, this immune response is often not strong enough to be able to cure tumours, and even when it is, its effect is limited to the area that has been irradiated. Now, however, research to be presented to the ESTRO 35 conference has shown that the addition of an immune system-strengthening compound can extend the radiation therapy-induced immune response against the tumour sites and that this response even has an effect on tumours outside the radiation field.
Ms Nicolle Rekers, MSc, from the Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands, will describe to the conference how a combination of radiation therapy and L19-IL2, an immunotherapy agent, can increase significantly the immune response when given to mice with primary colorectal tumours. L19-IL2 is a combination of an antibody that targets the tumour blood vessels and a cytokine, a small protein important in cell signalling in the immune system.
The researchers found not only that the mice were tumour-free following treatment, but also that when re-injected with cancer cells 150 days after cure, they did not form new tumours. There was also an increase in the number of cells with an immunological memory.