The Stago Group recently announced that it has completed the acquisition of HemoSonics LLC, a company specialized in the development of innovative point-of-care testing solutions based in Charlottesville, VA, with facilities in Durham, NC (USA). With the acquisition of the patented SEER technology (Sonic Estimation of Elasticity via Resonance) and its associated Quantra™ Hemostasis Analyser, Stago demonstrates its willingness to develop a point-of-care offering to complete its leadership in hemostasis testing and beyond. This transaction provides Stago with expanded opportunities for future growth and is an important part of the company’s on-going efforts to diversify its portfolio of medical devices in an ever-changing healthcare environment. “This significant step makes us very proud to contribute to the management of healthcare costs and to the improvement of patients outcomes worldwide”, says Lionel Viret, Chairman of the Board. “Stago brings exceptional expertise in the field of Thrombosis and Hemostasis that will greatly advance our efforts to rapidly and effectively deliver a new standard of care for the management of bleeding in the critical care setting” says Timothy Fischer, President and Chief Executing Officer of HemoSonics. Ferghana Partners acted as exclusive financial advisor to HemoSonics for this transaction.
www.stago.com
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For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger Institute and their collaborators adapted a technique from the field of evolution to confirm that, on average, 1 to 10 mutations are needed for cancer to emerge. The results also show the number of mutations driving cancer varies considerably across different cancer types. In the study, the team developed an approach to discovering which genes are implicated in cancer evolution and how many mutations in those genes drive cancer. In the future, such approaches could be used in the clinic to identify which few mutations in an individual patient are driving his or her cancer, from amongst the thousands of mutations present. Over 150 years ago, Charles Darwin described how different species evolve through the process of natural selection. Cancers also develop by natural selection, acting on the mutations that accumulate in the cells of our bodies over time. In this study, scientists applied an evolutionary perspective to quantifying natural selection in 7,664 tumours across 29 different cancers. One of the striking findings of the study was that mutations are usually well-tolerated by cells in the body. This was surprising because mutations that individuals inherit from their parents are often poorly tolerated, and are generally lost from the human species over time. In the body’s cells, however, as a cancer develops, nearly all mutations persist without impacting on the survival of the cell. The team also catalogued the main cancer genes responsible for 29 different cancer types. Researchers discovered several new cancer genes and determined how complete the current lists of cancer genes are. “We have addressed a long-standing question in cancer research that has been debated since the 1950s: how many mutations are needed for a normal cell to turn into a cancer cell? The answer is – a small handful. For example, about four mutations per patient on average drive liver cancers, whereas colorectal cancers typically require 10 or so driver mutations.” Dr Peter Campbell, lead author on the study, from the Wellcome Trust Sanger Institute “In the study, we revealed that around half of these key mutations driving cancer occur in genes that are not yet identified as cancer genes. There is already much insight into the most important genes involved in cancer; but there are many more genes yet to be discovered. We will need to bring together even larger numbers of cancers studied by DNA sequencing, into the tens of thousands, to find these elusive genes.”
Sanger Institute www.sanger.ac.uk/news/view/1-10-mutations-are-needed-drive-cancer-scientists-find
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In a bid to detect cancers early and in a non-invasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early-stage colorectal, breast, lung and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumours and other altered DNA that can be mistaken for cancer biomarkers. “This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high accuracy sequencing method is a promising approach to achieve this goal,” says Victor Velculescu, M.D., Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center. Blood tests for cancer are a growing part of clinical oncology, but they remain in the early stages of development. To find small bits of cancer-derived DNA in the blood of cancer patients, scientists have frequently relied on DNA alterations found in patients’ biopsied tumour samples as guideposts for the genetic mistakes they should be looking for among the masses of DNA circulating in those patients’ blood samples. To develop a cancer screening test that could be used to screen seemingly healthy people, scientists had to find novel ways to spot DNA alterations that could be lurking in a person’s blood but had not been previously identified. “The challenge was to develop a blood test that could predict the probable presence of cancer without knowing the genetic mutations present in a person’s tumour,” says Velculescu. The goal, adds Jillian Phallen, a graduate student at the Johns Hopkins Kimmel Cancer Center who was involved in the research, was to develop a screening test that is highly specific for cancer and accurate enough to detect the cancer when present, while reducing the risk of “false positive” results that often lead to unnecessary over-testing and overtreatments. The task is notably complicated, says Phallen, by the need to sort between true cancer-derived mutations and genetic alterations that occur in blood cells and as part of normal, inherited variations in DNA. As blood cells divide, for example, Velculescu says there is a chance these cells will acquire mistakes or mutations. In a small fraction of people, these changes will spur a blood cell to multiply faster than its neighbouring cells, potentially leading to pre-leukemic conditions. However, most of the time, the blood-derived mutations are not cancer-initiating. His team also ruled out so-called “germline” mutations. While germline mutations are indeed alterations in DNA, they occur as a result of normal variations between individuals, and are not usually linked to particular cancers. To develop the new test, Velculescu, Phallen and their colleagues obtained blood samples from 200 patients with breast, lung, ovarian and colorectal cancer. The scientists’ blood test screened the patients’ blood samples for mutations within 58 genes widely linked to various cancers. Overall, the scientists were able to detect 86 of 138 (62 percent) stage I and II cancers. More specifically, among 42 people with colorectal cancer, the test correctly predicted cancer in half of the eight patients with stage I disease, eight of nine (89 percent) with stage II disease, nine of 10 (90 percent) with stage III and 14 of 15 (93 percent) with stage IV disease. Of 71 people with lung cancer, the scientists’ test identified cancer among 13 of 29 (45 percent) with stage I disease, 23 of 32 (72 percent) with stage II disease, three of four (75 percent) with stage III disease and five of six (83 percent) with stage IV cancer. For 42 patients with ovarian cancer, 16 of 24 (67 percent) with stage I disease were correctly identified, as well as three of four (75 percent) with stage II disease, six of eight (75 percent) with stage III cancer and five of six (83 percent) with stage IV disease. Among 45 breast cancer patients, the test spotted cancer-derived mutations in two of three (67 percent) patients with stage I disease, 17 of 29 (59 percent) with stage II disease and six of 13 (46 percent) with stage III cancers. They found none of the cancer-derived mutations among blood samples of 44 healthy individuals. Despite these initial promising results for early detection, the blood test needs to be validated in studies of much larger numbers of people, say the scientists.
John Hopkins Medicinehttp://tinyurl.com/yd8vb763
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Researchers at the University of Birmingham have identified inflammatory biomarkers which indicate whether the brain has suffered injury. The team, led by Professor Antonio Belli, at the University’s College of Medical and Dental Sciences, now hopes to use these new biomarkers to develop a test which can be used on the side of a sports pitch or by paramedics to detect brain injury at the scene of an incident. Dr Lisa Hill, of the Institute of Inflammation and Ageing at the University of Birmingham, said: “Traumatic brain injury (TBI) is the leading cause of death and disability among young adults and, according to the World Health Organization, by 2020 TBI will become the world’s leading cause of neurological disability across all age groups. “Early and correct diagnosis of traumatic brain injury is one of the most challenging aspects facing clinicians. “Being able to detect compounds in the blood which help to determine how severe a brain injury is would be of great benefit to patients and aid in their treatment. “Currently, no reliable biomarkers exist to help diagnose the severity of TBI to identify patients who are at risk of developing secondary injuries that impair function, damage other brain structures and promote further cell death. “Thus, the discovery of reliable biomarkers for the management of TBI would improve clinical interventions.” Inflammatory markers are particularly suited for biomarker discovery as TBI leads to very early alterations in inflammatory proteins. In this novel study blood samples were taken from 30 injured patients within the first hour of injury prior to the patient arriving at hospital. Subsequent blood samples were taken at intervals of four hours, 12 hours and 72 hours after injury. These blood samples were then screened for inflammatory biomarkers which correlated with the severity of the injury using protein detection methods. In the laboratory, the team used a panel of 92 inflammation-associated human proteins when analysing the blood samples, which were screened simultaneously. The serum biomarkers were analysed from patients with mild TBI with extracranial injury, severe TBI with extracranial injury and extracranial injury only and all groups were compared to a control group of healthy volunteer patients. The results identified three inflammatory biomarkers, known as CST5, AXIN1 and TRAIL, as novel early biomarkers of TBI. CST5 identified patients with severe TBI from all other cohorts and, importantly, was able to do so within the first hour of injury. AXIN1 and TRAIL were able to discriminate between TBI and uninjured patient controls in under an hour. Dr Valentina Di Pietro, also of the Institute of Inflammation and Ageing at the University of Birmingham, said: “Early and objective pre-hospital detection of TBI would support clinical decision making and the correct triage of major trauma. “Moreover, the correct diagnosis of TBI, which is one of hardest diagnosis to make in medicine, would allow clinicians to implement strategies to reduce secondary brain injury at early stage, for example, by optimising blood and oxygen delivery to the brain and avoiding manoeuvres that could potentially increase intracranial pressure. “In addition, this has potential implications for drug development, as novel compounds could be given immediately after injury and potentially commenced at the roadside, if there was sufficient confidence in the diagnosis of TBI. “We conclude that CST5, AXIN1 and TRAIL are worthy of further study in the context of a pre-hospital or pitch-side test to detect brain injury.”
University of Birmingham www.birmingham.ac.uk/news/latest/2017/07/researchers-identify-inflammatory-biomarkers-indicating-brain-injury.aspx
HORIBA Medical and Siemens Healthineers have entered into a long-term agreement. The companies will collaborate in bringing new and innovative hematology solutions to the market globally. With HORIBA Medical as the original equipment manufacturer to complement the Siemens Healthineers portfolio, the companies will provide customers with expanded options to fulfill their hematology and multidisciplinary solution needs.
“With our commercial strength and global installed base of customers combined with HORIBA Medical’s innovative technologies, the relationship will expand the hematology solutions available to laboratories for diagnostics testing worldwide,” said Franz Walt, President, Laboratory Diagnostics, Siemens Healthineers.
“Our long-term vision and continuous investments coupled with our outstanding employees have resulted in innovative hematology technology solutions. I am extremely pleased that this long-term vision has resulted in an alliance with Siemens Healthineers” said Mr. Atsushi Horiba, Chairman, President & CEO of HORIBA, Ltd.
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For nearly 20 years, Tatyana Golovkina, PhD, a microbiologist, geneticist and immunologist at the University of Chicago, has been working on a particularly thorny problem: Why are some people and animals able to fend off persistent viral infections while others can’t? Mice from a strain called I/LnJ are especially good at this. They can control infection with retroviruses from very different families by producing specific antibodies that coat viruses and render them innocuous. Golovkina, a Professor of Microbiology, was interested in what makes these mice special, so she began searching for the genes responsible for their remarkable immune response. In a new study she and her colleagues identify this gene. They also began to uncover more clues how it might work to control anti-virus immune responses. Using a process called positional cloning, in which researchers progressively narrow down the location of a gene on the chromosome, they pinpointed it within the major histocompatibility complex (MHC) locus. The MHC locus is a well-known region of the genome involved with the immune system so it makes sense that the gene was located there, but this was a disconcerting discovery. “It was a bummer at first because there are tons of genes within the MHC locus all controlling immune response, not only against viruses, but also many other microbial pathogens and non-microbial disorders,” she said. “Most of the time when people map a gene to the MHC they give up and stop there, with an assumption that the gene encodes for one of the two major MHC molecules, MHC class I or and MHC class II.” But with the help of a biochemist, Lisa Denzin from Rutgers University, and a computational biologist, Aly Khan from the Toyota Technological Institute at Chicago, Golovkina and her team identified a gene called H2-Ob that enables this resistance. Together with another gene called H2-Oa, it makes a molecule called H2-O in mice and HLA-DO in humans. H2-O has been known for years as a negative regulator of the MHC class II immune response, meaning that it shuts down the immune response. Most researchers thought it was there to prevent autoimmune responses, which attack the body’s own tissues. But in this case, none of the I/LnJ mice showed signs of autoimmunity, so H2-O must have another purpose. Golovkina and her team discovered another interesting thing when they crossed I/LnJ mice that were resistant to infections with ones that were more susceptible. The resultant F1 mice were susceptible to infection. This indicated that the I/LnJ H2-Ob gene was recessive; both parents had to have a copy of the mutated gene to pass it on their offspring, and the product of the gene should be a non-functional protein. “That was really surprising,” Golovkina said. “Almost all pathogen-resistant mechanisms discovered so far are dominant, meaning that something needs to be gained to resist.” The immune system response to a virus in susceptible mice lasts three to four weeks, then the H2-O molecule tells it to stop. But the I/LnJ mice, which respond vigorously to infections, have a mutation on H2-Ob that makes it inactive. So, after they launch an immune response, it never shuts off. This keeps persistent retroviruses in check. Golovkina hypothesizes that while letting the immune response keep running may keep chronic infections in check, such as retroviruses or hepatitis B and C, other pathogens like tuberculosis can take advantage of a persistent immune response because they can get access to certain cells when they’re coated with antibodies (and I/LnJ mice happen to be susceptible to TB and produced anti-TB antibodies). At some point during the evolution of these genes, it was more advantageous to be able to switch off the immune response to some infections (such as intracellular bacterial pathogens), but it came at the cost of not being able to fight other long-term infections. Now that her team has identified the gene underlying anti-retrovirus and potentially anti-hepatitis B and C responses, Golovkina says that further research should be done to create genetic therapies to manipulate the function of this gene, or develop molecules that could interfere with the function of H2-O to allow the virus-specific response in chronically infected people.
University of Chicago Medicine sciencelife.uchospitals.edu/2017/08/15/scientists-identify-gene-that-controls-immune-response-to-chronic-viral-infections/
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When performed in tandem, two molecular biology laboratory tests distinguish, with near certainty, pancreatic lesions that mimic early signs of cancer but are completely benign. The lesions almost never progress to cancer, so patients may be spared unnecessary pancreatic cancer screenings or operations. The two-test combination is the only one to date that can accurately and specifically identify these benign pancreatic lesions. Its utility was described in one of the largest studies of patients with this form of pancreatic lesion by researchers from Indiana University, Indianapolis. Between 2 to 3 percent of all patients have some type of pancreatic lesions or cysts revealed on routine abdominal diagnostic radiology scans. Nearly all of these patients will later develop pancreatic cancer. The most common and deadliest form of pancreatic cancer—pancreatic adenocarcinoma—has a five-year survival rate of 12 to 14 percent for early-stage disease and 1 to 3 percent for advanced disease, according to the American Cancer Society. A small percentage of patients have serous cystic neoplasms (SCN) that do not harbour malignant potential or progress to cancer. Nevertheless, these patients undergo imaging or other surveillance every six months to spot changes indicative of cancer, or they undergo an operation to remove part of the gland as a precaution because SCN are difficult to find using standard diagnostic methods. More than 60 percent of SCN are not predicted preoperatively3 and 50 to 70 percent are missed or incorrectly diagnosed on radiology scans.4 However, the researchers determined that two proteins can play a significant role in ruling out pre-cancer and cancer. Vascular endothelial growth factor A (VEGF-A) is a protein associated with promotion of new blood vessel formation. VEGF-A is upregulated in many tumours, and its expression can be correlated with a tumour’s stage. Its utility in the diagnosis of pancreatic cysts was discovered by researchers at Indiana University. Carcinoembryonic antigen (CEA) is a protein associated with cell adhesion. It is present in low levels in healthy individuals, but it is increased with certain types of cancers. Tests for each of these proteins in pancreatic cyst fluid have accurately distinguished SCN from other types of pancreatic lesions. In the present study, VEGF-A, alone, singled out SCN with a sensitivity of 100 percent and specificity of 83.7 percent, and CEA had a 95.5 percent sensitivity and 81.5 percent specificity. Together, however, the tests approached the gold standard of pathologic testing: The combination had a sensitivity of 95.5 percent and specificity of 100 percent for SCN. Authors of the study concluded that results of the VEGF-A/CEA test could have prevented 26 patients from having unnecessary surgery.
American College of Surgeons www.facs.org/media/press-releases/2017/pancreatic062217
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Over the past decade, mutations in more than 60 different genes have been linked with autism spectrum disorder, including de novo mutations, which occur spontaneously and aren’t inherited. But much of autism still remains unexplained. A new study of nearly 6,000 families implicates a hard-to-find category of de novo mutations: those that occur after conception and therefore affect only a subset of cells. De novo mutations can occur in a parent’s sperm or egg. Alternately, they can occur after egg and sperm meet, arising in an embryonic cell. These are known as somatic mutations or post-zygotic mutations (PZMs). If a PZM happens very early, when the embryo has just a handful of cells, the mutation will show up in most of the mature organism’s cells. But the later PZMs occur during embryonic development, the fewer cells will carry them, making them harder to detect. “If the mutation is in a very small fraction of all cells, it will be missed by whole-exome sequencing,” said Elaine Lim, a postdoctoral fellow in the lab of Christopher A. Walsh, the Bullard Professor of Pediatrics and Neurology at Harvard Medical School and Boston Children’s Hospital. Lim is first author of the study; Walsh is the senior investigator. To identify PZMs, Lim, Walsh and colleagues obtained whole-exome sequencing data previously gathered from 5,947 families, usually through blood tests, courtesy of the Simons Foundation Autism Research Initiative Simplex Collection, the Autism Sequencing Consortium and Autism Speaks. They then re-sequenced some of the DNA from these children using three independent sequencing technologies in parallel. Based on their findings, they classified 7.5 percent of autism spectrum disorder subjects’ de novo mutations as PZMs. Of these, 83 percent had not been picked up in the original analysis of their genome sequence. Some PZMs affected genes already known to be linked to autism or other neurodevelopmental disorders (such as SCN2A, HNRNPU and SMARCA4) but sometimes affected these genes in different ways. Many other PZMs occurred in genes known to be active in brain development (such as KLF16 and MSANTD2) but not previously associated with autism spectrum disorder. The connection of these genes to autism may have been missed because the earlier studies focused on mutations that knocked down gene function, the authors said. “Some of the postzygotic mutations we found represented a gain of function, not a loss of function,” said Lim, who is also affiliated with the Wyss Institute for Biologically Inspired Engineering. Lim, Walsh and colleagues then brought in another huge data set: gene expression data from the BrainSpan project. These publicly available data came from autopsies of brain samples from deceased patients of different ages, from prenatal through adult. Comparing these with the genomic sequencing data, based mostly on blood DNA samples, allowed the researchers to estimate the timing of the PZMs and the brain regions they affected. “By overlapping the data, we can start to map where in the brain these genes are expressed and when the mutations occurred during development,” said Lim. These analyses showed that PZMs in the subjects with autism spectrum disorder occur disproportionately in genes expressed in the amygdala. “This was exciting to us, in that the amygdala has been proposed as an important region of the brain in autism,” said Lim. Overall, the work adds to the evidence that complex brain disorders, such as epilepsy, intellectual disability, schizophrenia and brain malformations, can arise from non-inherited mutations that occur at some point during prenatal development.
Harvard Medical Schoolhttp://tinyurl.com/yb2lpxd7
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Houston Methodist cancer researchers are now closer to creating a blood test that can identify breast cancer patients who are at increased risk for developing brain metastasis, and also monitor disease progression and response to therapy in real time. The discovery of identifying a distinct group of cells in the bloodstream of patients who have breast cancer brain metastases could lead to the creation of more sensitive screening tools. A proof-of-concept study led by Dario Marchetti, Ph.D., detected a distinct group of circulating tumour cells (CTCs) associated with brain metastasis. The finding brings cancer researchers closer to understanding how the “seeds” of metastatic disease can thrive in breast cancer patients and cause it to spread to the brain. “Our research confirmed that CTCs in breast cancer brain metastases are distinct from other circulating tumour cells. Moreover, unlocking the mystery of how these seeds of metastatic disease survive and thrive over a period of years, sometimes decades, is an enigma in cancer,” said Marchetti, senior author and director of the Biomarker Research Program at Houston Methodist Research Institute. “Now we can take this information and develop a more sensitive screening tool to detect metastatic cancer in the blood, possibly even before metastasis is radiologically detectable by MRI.” Magnetic resonance imaging is the accepted standard-of-care to diagnose breast cancer brain metastasis (BCBM) in patients. However, in most cases, by the time MRI detects the metastatic mass, the cancer has progressed to a stage where few curative treatment options are available, leading to poor overall survival. According to extensive clinical studies, approximately 20 percent of breast cancer patients will develop brain metastasis over their lifetime, and, in general, metastatic disease to the brain is estimated to become the number one cancer killer within the next decade. “Our lab is the first in this field to perform a comprehensive report of patient-derived circulating tumour cells at the gene expression level, so we now have a clearer picture of the signalling pathways that allows them to establish brain metastases. By comparing the whole genome expression patterns of CTCs isolated from patient blood samples diagnosed with or without BCBM, we uncovered a 126 gene-signature that is specific to these brain metastatic CTCs,” said Debasish Boral, Ph.D., the paper’s first author and a research associate with the Biomarker Research Program at Houston Methodist Research Institute. This research builds on a 2015 research paper where Marchetti’s lab isolated four distinct circulating tumour cell subsets that were implicated in breast cancer cell dormancy. Viable breast cancer cells can remain dormant in the patients’ bone marrow or other organs like the brain, lungs and liver, even decades after a primary tumour is surgically removed. These scattered cells are often undetectable by traditional clinical tools, making it nearly impossible to detect and treat metastatic disease while still amenable to therapy. The Houston Methodist researchers are now focused on broadening the study patient population, with the end goal of transforming this information into the development of two kinds of non-invasive liquid biopsies that could be used by treating physicians: a screening method to predict brain metastasis before the disease is detectable by current diagnostic standards (MRI); and another to monitor treatment efficacy in real-time in those patients diagnosed with brain metastasis.
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Tens of thousands of cancer patients each year may benefit from an immunotherapy regimen called PD-1 blockade, based on results from a new clinical study. The findings establish genetic markers that help physicians identify which patients might respond to the therapy, which had been approved previously for a select few classes of cancer. "What we describe in this paper applies to about 4% of patients with advanced cancer, regardless of the tumour type," said Bert Vogelstein of Johns Hopkins University, a senior author on the paper. In an 86-patient clinical trial encompassing 12 different kinds of cancers, Dung Le and colleagues at Johns Hopkins University demonstrated that the immunotherapy drug pembrolizumab (an anti-PD-1 antibody) was effective against multiple types of tumours. All of the patients had cancers with defects in a genome maintenance pathway called mismatch repair (MMR). "One patient, a young graduate student, was scheduled to go into hospice for terminal care two days prior to receiving the test result that showed he had an MMR-deficient tumour," said Vogelstein. "Shortly after beginning treatment, he went into remission. Since then he’s been able to finish his Ph.D., get married and live a happy and productive life." PD-1 blockade doesn’t directly destroy tumours, but instead aids the immune system in targeting cancer cells — which can suppress the body’s defences in order to thrive. Until recently, PD-1 blockade therapies were approved for only a select few classes of cancers, such as melanoma and lung cancer. Yet in a historic May 2017 decision , the United States Food and Drug Administration ruled that tumour genetics, rather than tissue of origin, could be used as a clinical indicator for pembrolizumab therapy. "This is the first approval for a treatment that is tissue agnostic, which means clinicians can use pembrolizumab for any tumour with mismatch repair deficiency," said Le. As many as 60,000 cancers every year might harbour MMR mutations that would render them susceptible to PD-1 blockade, according to Le and colleagues’ analysis of genome sequencing data from 12,019 cancers representing 32 distinct tumor types. PD-1 blockade takes advantage of the fact that MMR defects make cancer genomes inherently unstable, giving them a potential Achilles’ heel. "Tumours that have more chaotic genomes produce more proteins that are recognized by the immune system," said Geoff Lindeman, a breast cancer researcher at Walter and Eliza Hall Institute of Medical Research, who was not involved in the study. Different types of cancers experience various levels of genomic chaos. Most tumors harbor roughly 50 genetic alterations whereas skin and lung cancers tend to have mutation counts well in the hundreds, arising from exposure to environmental DNA-damaging agents like UV light or cigarette smoke. Problems with MMR can push tumors towards thousands of mutations per cell. Yet even with such high mutational loads, cancer can still escape from the immune system. "Tumors find ways to switch off the immune cells," said Vogelstein. "Checkpoint inhibitors like anti-PD-1 can re-awaken these immune cells for an extra weapon in the ongoing war between cancer and the immune system." Though the trial is still ongoing, 11 patients were able to stop taking the therapy; they have remained disease-free with no evidence of recurrence for an average of 8.3 months.
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