Tag: pancreatic cancer

Categories : Cancer Surgeries & ProceduresTags :

Targeted Radiation During Surgery Reduces Pancreatic Cancer Recurrence

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Image of a what is targeted with radiation. Red represents the pancreatic tumor, which is contacting with a major nearby artery. Yellow represents the Baltimore Triangle, which is now targeted in all patients, in addition to red volume. Credit: Amol Narang, M.D.

Using targeted radiation during surgery – referred to as intraoperative radiation – to eliminate pancreatic cancer cells that have spread to areas around the pancreas, investigators at Johns Hopkins have been able to reduce the recurrence rate around the pancreas to 5%. This is believed to be the lowest ever reported for this population of patients, according to a preliminary study by the team from the Johns Hopkins Kimmel Cancer Center.

The study was presented at the American Society for Radiation Oncology annual meeting in September 2025.

The study enrolled 20 patients with borderline resectable or locally advanced pancreatic cancer. Patients received presurgical chemotherapy and radiation targeted to shrink the tumours away from the blood vessels. Then, during surgery to remove their tumours, patients received another dose of precisely targeted radiation using a robotic device that carries small radioactive beads inserted through catheters. The device enabled the team to pinpoint a triangular area near the pancreas, where recurrences commonly occur. Only one of the 20 patients experienced a recurrence around the pancreas at the 24-month mark – a major achievement for a cancer that, until recently, had lagged behind other cancers in treatment success.

By the time most pancreatic cancers are diagnosed, the tumours have spread to affect important blood vessels around the pancreas. Historically, patients with pancreatic cancers whose blood vessels were affected could not undergo surgical removal of their tumours. But in the past decade, clinicians at the Johns Hopkins Kimmel Cancer Center’s Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care have pioneered new approaches that use chemotherapy and radiation to shrink the tumours away from blood vessels, enabling more patients to undergo surgical removal of their tumours.

However, many of these patients continued to experience tumor recurrences, and Amol Narang, M.D., associate professor of radiation oncology and molecular radiation sciences, and his colleagues sought to determine why.

The team learned that the pancreatic cancer cells were spreading along nerves near the pancreas to a fatty, nerve-dense triangular area just above the pancreas, which Narang calls the “Baltimore triangle.” When he and his colleagues started targeting the Baltimore triangle with radiation before surgery to kill these stray cancer cells, pancreatic cancer recurrence rates in their patients dropped from 47% to 12% at two years post-surgery. Yet, in the 12% who experienced recurrences around the pancreas, the recurrences continued to occur in the Baltimore triangle.

To further lower recurrence rates, Narang and his colleagues decided to deliver an additional round of Baltimore triangle-targeted radiation to patients during surgery after removal of the pancreatic tumour. He explained that, during the surgery, surgeons remove a part of the duodenum, next to the pancreas, making it easier to access the Baltimore triangle without risking harm to surrounding organs. The combination of radiation targeted to the Baltimore Triangle prior to surgery as well as intraoperative radiation to the triangle during surgery allowed Narang to deliver ablative doses of radiation to this region.

“The combination of intraoperative radiation and targeting the Baltimore triangle has gotten us to a 5% recurrence rate, which is the lowest-ever reported recurrence rate around the pancreas for this population of patients to our knowledge. But I think we can drop to 0% in our next study,” Narang says. “We must do whatever we can to prevent recurrences from happening, because when pancreatic cancer comes back, it is often incurable. These results give us hope, though, that this can be done for a cancer where even decade ago, most thought this wasn’t possible.”

The only recurrence in the study occurred in the part of the Baltimore triangle that the team had difficulty reaching during the intraoperative treatment. Currently, the team is developing strategies to target this hard-to-reach part of the triangle, with the hopes of reducing recurrences to zero. Once they’ve mastered that refined approach, they would like to team up with other cancer centres across the US to run a larger clinical trial to confirm their results. 

Source: Johns Hopkins Medicine

Categories : CancerTags :

Pancreatic Cancer Forms ‘Synapses’

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Immunofluorescence image of pancreatic cancer cells that invade nerves: nerve cells appear in green, tumor cells in red.

Pancreatic cancer is one of the deadliest types of tumours. A team at the Technical University of Munich (TUM) has discovered that pancreatic tumours exploit the body’s nervous system by forming so-called pseudosynapses. Through a specific receptor, the cancer cells take up the neurotransmitter glutamate, which drives tumour growth. The researchers now hope to identify drugs that can block this process in patients.

It has been known for some time that the nervous system can affect cancer development. For example, nerve cells from healthy tissue can grow into tumors, a phenomenon known as “neural invasion,” which is typically linked to a poor prognosis.

About six years ago, a US research group discovered a new mechanism in the brain: tumours can form their own synapses, co-opting neuronal communication for their benefit. Professor Ekin Demir, a clinician scientist at the Department of Surgery at the TUM University Hospital, and his team built on this finding to investigate whether tumours outside the brain might form similar structures.

Searching for “tumour synapses”

Pancreatic tumours often show neural invasion. Thus, if such synapse-like structures existed outside the brain, this was the most likely place to find them. The researchers searched pancreatic tumour tissue for clusters of receptors specialised for specific neurotransmitters. In some samples, they did indeed find a strong concentration of NMDA receptors – the receptors that bind glutamate. Then came the successful search for the characteristic structures of synapses, carried out in the classic way under the electron microscope Owing to subtle physiological differences compared with typical neuronal synapses, the researchers refer to these structures as pseudosynapses.

Calcium waves promote tumour growth

What advantage do pancreatic tumours gain by forming pseudosynapses? Like other glands, the pancreas is regulated by the nervous system. Depending on the body’s needs healthy pancreatic cells receive the neurotransmitter glutamate through their synapses. This triggers a series of processes. Pseudosynapses exploit this natural mechanism. “When glutamate binds to the cancer cells’ NMDA receptors, a channel opens and calcium flows into the cell,” explains Professor Demir. “This influx triggers molecular signalling cascades that drive tumour growth and metastasis.” The team observed that the cancer cells generate characteristic slow, long-lasting calcium waves that drive tumour growth in a sustained way.

Yet this remarkable mechanism may open up a path to new cancer therapies. In mouse experiments, the researchers successfully blocked the NMDA receptors on tumour cells with a drug. The result: pancreatic tumours grew more slowly, developed fewer metastases, and the animals lived longer.

“We are currently using bioinformatic methods to identify approved drugs that, in addition to their primary effects, can also block these specific NMDA receptors in pancreatic cancer cells,” says Professor Ekin Demir. “Therapies targeting the interface between the nervous system and tumours could open up entirely new treatment options.” The team suspects that other tumour types may also form pseudosynapses to accelerate their growth.

The study is published in Cancer Cell.

Source: Technical University of Munich

Categories : CancerTags :

Acidic Tumour Environment Promotes the Survival and Growth of Cancer Cells

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Cancer cells reshape their mitochondria (stained yellow) when exposed to acidosis. The composed image shows two cells under neutral pH (left) compared to an acidic environment (right), where mitochondria form elongated networks.

Tumours are not a comfortable place to live: oxygen deficiency, nutrient scarcity, and the accumulation of sometimes harmful metabolic products constantly stress cancer cells. A research team from the German Cancer Research Center (DKFZ) and the Institute of Molecular Pathology (IMP) in Vienna has now discovered that the acidic pH value in tumour tissue – known as acidosis – is a decisive factor in how pancreatic cancer cells adapt their energy metabolism to survive these adverse conditions. The results were published in the journal Science.

Poor blood circulation and increased metabolic activity often create hostile conditions in tumours: typical symptoms include a lack of oxygen, glucose, and other nutrients, the accumulation of sometimes harmful metabolites, and acidification of the tumour environment, known as acidosis.

The team led by Wilhelm Palm from the DKFZ and Johannes Zuber from the IMP investigated how cancer cells adapt to these harsh conditions. First, the researchers systematically switched off each gene individually in pancreatic cancer cells using the CRISPR-Cas9 gene editing tool and then tracked how its loss affected the survival and growth of the cells under defined stress conditions. These experiments were initially conducted in culture dishes. The genes identified using this approach were then specifically switched off in mice with pancreatic cancer, and the effects were compared with the results from the cell culture.

The comparative analysis of hundreds of such genes relevant to cancer cell growth under stress conditions surprisingly showed that the metabolism of cancer cells in the mouse model was strongly influenced by adaptations of their energy balance to tumour acidosis. The metabolism of cancer cells within a tumour differs significantly from that in conventional cell culture and can best be replicated by an acidic environment.

“It is not just the lack of oxygen or nutrients that changes the metabolism in the tumour – it is primarily the acidification of the tumour environment,” explains Wilhelm Palm. Acidosis helps cancer cells switch from sugar-based energy production (glycolysis) to more efficient energy production through respiration in the mitochondria. These cell structures, known as organelles, are also referred to as the “powerhouses of the cell.”

The researchers were able to show that the acidic pH value triggers profound changes in the mitochondria. Normally, they are present in cancer cells as small, fragmented structures. Under acidic conditions, however, they merge into extensive networks that are significantly more efficient.

This is possible because acidosis inhibits the activity of the signalling protein ERK. Overactivation of this signalling pathway normally causes mitochondria in cancer cells to repeatedly divide into many small fragments. If this fragmentation does not occur as a result of tumour acidosis, mitochondria can use various nutrients more efficiently for energy production. If genetic intervention prevents the mitochondria from fusing, cancer cells lose their metabolic flexibility and grow much more slowly in the acidic environment of a tumour.

“Our results show that acidosis is not simply a by-product of tumour metabolism, but an important switch that controls the energy supply and survival strategies of cancer cells,” explains co-study leader Johannes Zuber. In the long term, these findings could open up new avenues for therapies that specifically target the energy metabolism of tumours.

Source: German Cancer Research Center

Categories : Cancer Lab Tests and ImagingTags :

Preventing Unnecessary Pancreatic Cancer Surgery

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Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Pancreatic cysts are fluid-filled sacs that can form in the pancreas. Some remain benign, while others have the potential to develop into pancreatic cancer. A recent study, which followed 257 patients in Japan for an average of five years, showed that the presence or absence of invasive nodules in pancreatic cysts is key to assessing whether these cysts are benign or cancerous.

The findings, published in the journal Annals of Surgery, may help patients diagnosed with a high risk of pancreatic cancer to avoid unnecessary surgery.

Pancreatic cancer is one of the most life-threatening and rapidly growing cancers. Pancreatic cysts, known as pancreatic intraductal papillary mucinous neoplasms (IPMNs), are gaining attention as one of the precursors of the cancer that can be identified by radiological imaging. In this context, patients diagnosed with pancreatic cysts are referred for further evaluation, and if they meet the criteria for being at particularly high risk of developing cancer, called high-risk stigmata, they are often recommended for surgery.

However, it was not clear whether all patients who met the criteria would need to undergo surgery. “In fact, among patients who underwent surgery, there were a number of cases where pathological examination results showed that their IPMNs were still benign and had not progressed to cancer,” explained Ryohei Kumano from Nagoya University, the first author of the study. “Pancreatic surgery is a significant burden for patients, so we wanted to find a more accurate way to diagnose whether their IPMNs are benign or cancerous in order to avoid unnecessary surgery.”

A research group consisting of Professor Hiroki Kawashima and Dr Kumano from Nagoya University Graduate School of Medicine, Professor Eizaburo Ohno from Fujita Health University, and their colleagues focused on the presence or absence of invasive nodules in 257 IPMN patients with high-risk stigmata. The researchers evaluated the prognosis of the patients with and without these nodules.

Invasive nodules, solid growths within cysts that have begun to invade surrounding tissues, are difficult to detect with a conventional method that uses a CAT scan. Therefore, the researchers instead used contrast-enhanced endoscopic ultrasound, which is thought to detect invasive nodules more accurately.

To track the prognosis of patients with and without invasive nodules between surgical and non-surgical groups, the researchers followed them for an average of about five years (ranging from 6 months to 24 years, depending on the patient).

The results showed that the presence or absence of invasive nodules had a significant impact on their survival. For patients with invasive nodules, undergoing surgery had a positive effect on improving their survival. On the other hand, most patients without invasive nodules had a favorable outcome even without surgery. 

Endoscopic ultrasound (EUS) enables differentiation between non-invasive and invasive nodules within IPMN, providing crucial information for surgical decision making. (Credit: Ryohei Kumano) 

In this study, a total of 21 patients who did not have invasive nodules opted for clinical monitoring instead of surgery. Notably, their five-year survival rates were 84.7% for overall survival and 100% for disease-specific survival.

In addition, in patients at higher risk for surgery, such as the elderly, there was little difference in survival rates between patients who underwent surgery and those who did not, if they had no invasive nodules. “Avoiding surgery, especially in such patients, seems to be a reasonable treatment strategy, given the fact that pancreatic surgery is highly invasive, carries a high risk of complications, and requires a long recovery period,” Kumano said.  

“We expect that our findings will contribute to future clinical guidelines for IPMNs, leading to more accurate cancer diagnosis and optimised treatment selection.”

Source: Nagoya University

Categories : CancerTags :

Research Identifies the Key to Pancreatic Cancer’s Extreme Aggressiveness

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Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Pancreatic cancer is one of the most aggressive cancers and has one of the lowest survival rates: only 10% after five years. One of the factors contributing to its aggressiveness is its tumour microenvironment, known as the stroma, which makes up the bulk of the tumour mass and consists of a network of proteins and different non-tumour cells. Among these, fibroblasts play a key role, helping tumour cells to grow and increasing their drug resistance.

Now, a study led by researchers from the Hospital del Mar Research Institute and other institutions has identified a new key factor contributing to this feature of pancreatic cancer: a previously unknown function of Galectin-1 protein inside the nuclei of fibroblasts. This discovery, published in the journal PNAS, offers new insights into the role of these cells in the progression of pancreatic cancer.

“The stroma is considered a key component in the aggressive nature of pancreatic cancer, as it interacts with tumour cells, protects them, and hinders the action of drugs. Moreover, stromal cells, particularly fibroblasts, produce substances that support tumour growth and dissemination,” explains Dr Pilar Navarro, coordinator of the Cancer Molecular Targets Research Group at the Hospital del Mar Research Institute and IIBB-CSIC-IDIBAPS. Until now, fibroblasts were known to secrete Galectin-1, a protein with pro-tumour properties. This study, however, shows that the molecule is also located inside fibroblasts-specifically in their nuclei-where it plays a key role in gene expression regulation.

The presence of this molecule activates fibroblasts, making them support tumour cell development. The researchers also discovered that “Galectin-1 can regulate gene expression in these cells at a highly specific level without altering the DNA sequence, through epigenetic control. One of the genes it regulates is KRAS, which plays a critical role in pancreatic tumours,” explains Dr Navarro. This gene is also present in tumour cells in 90% of patients, though in this case it is mutated. It is considered one of the main drivers of uncontrolled growth and tumour aggressiveness.

Designing new strategies

The team behind the study had previously identified the prominent role of Galectin-1 in pancreatic cancer. The newly discovered functions now pave the way for developing new strategies to tackle this type of tumour. “Until now, efforts have focused on inhibiting Galectin-1 secreted by the stroma surrounding the tumour. Now, we see that we also need to block the protein inside the fibroblast nuclei,” says Dr Neus Martínez-Bosch, researcher at the Hospital del Mar Research Institute. “We need to find new inhibitors that work inside fibroblasts, not just on the protein they secrete,” she adds.

To carry out the study, researchers worked with tissue samples from pancreatic cancer patients, allowing them to analyse the presence and function of Galectin-1 in fibroblast nuclei. They also performed in vitro experiments with human fibroblast cell lines, investigating the effects of inhibiting both the protein and the KRAS gene, and observed deactivation of these cells-effectively halting their cooperation with tumour cells.

Dr. Judith Vinaixa, also a researcher at the Hospital del Mar Research Institute and first author of the study, highlights the importance of these results: “We have confirmed the key role of Galectin-1 in the fibroblast cell nucleus, where it regulates the expression of multiple genes critical for cell behaviour.”. Dr. Gabriel Rabinovich, researcher at IBYME (CONICET) and the CaixaResearch Institute, adds: “The next steps will involve exploring therapeutic combinations that inhibit both extracellular and intracellular Galectin-1. This protein also participates in key processes such as blood vessel formation and resistance to immunotherapy. Therefore, this strategy becomes particularly relevant given the multiple antitumoral effects of Galectin-1 inhibition.”

Source: IMIM (Hospital del Mar Medical Research Institute)

Categories : Cancer Lab Tests and ImagingTags :

New Blood Test for Pancreatic Cancer Exceeds Gold Standard

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Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

A recent double-blinded, peer-reviewed analysis published in Cancer Letters revealed that an experimental test for pancreatic cancer correctly identified 71% of lab samples compared to only 44% correctly identified by the current gold-standard test.

An experimental blood test for pancreatic cancer that was developed by teams led by VAI Professor Brian Haab, PhD, and Randall E. Brand, MD, a physician-scientist and professor of medicine at the University of Pittsburgh, created the test. This evaluation by a commercial laboratory is an important milestone toward making the test available for patients.

Before the new test can be used by doctors to diagnose cancer, it must undergo clinical validation. During this process, a CLIA-accredited diagnostics laboratory adapts the experimental test into a version that reliably works under the strict conditions in a clinical lab. CLIA is a rigorous federal standard that ensures lab quality.

“Validation studies are essential for transforming a test developed in an academic lab into one that is used to diagnose real people,” Haab said. “For a person being evaluated for pancreatic cancer, the stakes are high. Validation studies ensure that new tests work as intended.”

The new test works by detecting two sugars — CA199.STRA and CA19-9 — that are produced by pancreatic cancer cells and escape into the bloodstream. CA19-9 is the current gold-standard biomarker for pancreatic cancer. Haab’s lab identified CA199.STRA as a cancer biomarker and developed the technology to detect it.

The new test also greatly reduced the number of false negatives while maintaining a low false positive rate, according to the recent analysis. Low rates of false positives and false negatives are important because they reflect the test’s ability to correctly identify the presence or absence of cancer.

Clinical validation of the test will be conducted by ReligenDx, a CLIA-accredited diagnostics lab based in Pennsylvania. The process is expected to take two years.  

If successful in clinical validation, Haab envisions the test being used in two main ways: 1. Catching pancreatic cancer more quickly in people at high risk of the disease, which would enable earlier treatment and 2. Monitoring progression and treatment response in people diagnosed with pancreatic cancer.

Source: Van Andel Research Institute

Categories : CancerTags :

Adding Vitamin C to Chemotherapy Doubles Pancreatic Cancer Survival Time

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Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Results from a randomised, phase 2 clinical trial show that adding high-dose, intravenous (IV) vitamin C to chemotherapy doubles the overall survival of patients with late-stage metastatic pancreatic cancer from eight months to 16 months. 

“This is a deadly disease with very poor outcomes for patients. The median survival is eight months with treatment, probably less without treatment, and the five-year survival is tiny,” says Joe Cullen, MD, University of Iowa professor of surgery, and radiation oncology, and senior author of the study. “When we started the trial, we thought it would be a success if we got to 12 months survival, but we doubled overall survival to 16 months. The results were so strong in showing the benefit of this therapy for patient survival that we were able to stop the trial early.” 

The findings, published in Redox Biology, mark another success for high-dose, intravenous vitamin C, which has overcome many hurdles in the almost 20 years UI researchers have persevered to demonstrate its benefit for cancer patients. 

“We’ve had ups and downs of course, but this is a culmination of a lot of people’s hard work,” says Cullen who also is a member of UI Health Care Holden Comprehensive Cancer Center. “It’s really a positive thing for patients and for the University of Iowa.”

Increased survival, improved quality of life

In the study, 34 patients with stage 4 metastatic pancreatic cancer were randomized to receive either standard chemotherapy (gemcitabine and nab-paclitaxel), or the chemotherapy plus infusions of high-dose vitamin C. The results showed that average overall survival was 16 months for the patients receiving the chemotherapy plus vitamin C, compared to eight months for the patients getting just chemotherapy. In addition, progression free survival was extended from four months to six months. 

“Not only does it increase overall survival, but the patients seem to feel better with the treatment,” Cullen says. “They have less side effects, and appear to be able to tolerate more treatment, and we’ve seen that in other trials, too.” 

The new study is not the only evidence of the benefit of including IV vitamin C as part of cancer treatment. Earlier this year, the results of another UI phase 2 clinical trial in patients with glioblastoma, a deadly form of brain cancer, were published. That study also showed a significant increase in survival when high-dose, IV vitamin C was added to standard of care chemotherapy and radiation. Cullen was also part of that trial along with his colleague Bryan Allen, MD, PhD, UI professor and head of radiation oncology. 

A third phase 2 trial in non-small cell lung cancer is still underway, with results expected within the year. All three trials were funded by a 2018 grant from the National Cancer Institute (NCI). 

“This NCI funding was incredibly important for us to conduct these phase 2 trials and obtain these really encouraging results. Our aim is to show that adding high-dose, IV vitamin C, which is very inexpensive and very well tolerated, can improve treatment for these cancers that are among the deadliest affecting the U.S. population,” Cullen adds. 

A long journey to clinical trials

Cullen, Allen, and their colleagues at UI Health Care have been researching the anti-cancer effect of high-dose, IV vitamin C for decades. Their work revealed a critical difference between intravenous and oral vitamin C. Intravenous vitamin C administration produces very high levels in the blood, which cannot be achieved with oral delivery. These high concentrations result in unique chemical reactions within cancer cells that render the cell more vulnerable to chemo- and radiation therapies. 

Cullen notes that despite scepticism towards vitamin C as a cancer therapy, the results he and his colleagues have obtained, from basic science findings to understand the biological mechanisms at work, through the various clinical trials, have been highly encouraging and robust. 

“Through every step of the process, it continued to improve. We did it in cells, it worked great. We did it in mice, it worked great. Then our phase one trials looked very promising. So, the progression has just been phenomenal, really,” Cullen says. “For example, in one of our phase 1 trials for pancreatic cancer, where we combine high-dose, IV vitamin C with radiation, we still have three long-term survivors. They’re out nine years at this point, which is far beyond the typical survival range.” 

Source: University of Iowa Health Care

Categories : Cancer Surgeries & ProceduresTags :

Can Metabolic-bariatric Surgery help Prevent Pancreatic Cancer in Obesity?

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Sleeve gastrectomy. Credit: Scientific Animations CC4.0

Obesity and type 2 diabetes are risk factors for various malignancies, including pancreatic cancer, which has a high death rate. A new analysis in Diabetes/Metabolism Research and Reviews suggests that metabolic-bariatric surgery may lower the risk of developing pancreatic cancer in people with obesity, especially in those who also have type 2 diabetes.

In the systematic review and meta-analysis, investigators identified 12 relevant studies that explored the effects of metabolic-bariatric surgery on pancreatic cancer incidence, with a total of 3 711 243 adults with obesity. Surgery was associated with a 44% reduction in pancreatic cancer risk among individuals with obesity but without type 2 diabetes and a 79% risk reduction in those with both obesity and type 2 diabetes.

“Metabolic-bariatric surgery not only has beneficial effects on obesity and type 2 diabetes but also may play a crucial role in reducing the risk of pancreatic cancer in these individuals,” said corresponding author Angeliki M. Angelidi, PhD, of the Broad Institute of MIT and Harvard. “These findings underscore the need for further research to elucidate the underlying mechanisms and understand the full spectrum of health benefits of metabolic-bariatric surgery beyond weight loss.”

Source: Wiley

Categories : Cancer Immune SystemTags :

How Cancer Reprograms Immune Cells to Join the Enemy

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Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

Cancer has been described as “a wound that does not heal,” implying that the immune system is unable to wipe out invading tumour cells. A new discovery reported in PNAS confirms that a key molecule can reprogram immune cells into turncoats that promote cancer growth.

Studying the behaviour of these “pro-tumour” immune cells is important because they could be targets for therapies that block their harmful activity, said Minsoo Kim, PhD, corresponding author of the study and a research leader at the Wilmot Cancer Institute.

Kim led a team of scientists investigating the dynamic interactions that occur between cells in the tumor environment, and the underlying factors that cause the harmful transformation of immune cells from good to bad.

They found that PAF (platelet-activating factor) is the key molecule that controls the destiny of the immune cells. PAF not only recruits cancer-promoting cells, but it also suppresses the immune system’s ability to fight back. In addition, they found that multiple cancers rely on the same PAF signals.

“This is what could be most significant,” said Kim. “Because if we find a treatment that could interfere with PAF, it could potentially apply to many types of cancer.”

Much of the team’s work focused on pancreatic cancer cells. It is one of the most deadly cancers, with a five-year survival rate of about 12%, and is notoriously hard to treat because pancreatic tumours are surrounded by a toxic stew of proteins and other tissues that protect the cancer from the immune system’s natural role to attack invaders. They also studied breast, ovarian, colorectal, and lung cancer cells, using advanced 3D imaging technology to watch the behaviour of immune cells as they swarmed to the cancerous region.

Source: University of Rochester Medical Center

Categories : CancerTags :

Faster Detection of Pancreatic Cancer

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Glycopeptide probes detect tumour-associated antibodies in blood samples

Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Pancreatic cancer is one of the most lethal forms of cancer, primarily because it is usually diagnosed very late. Current markers are too insensitive and unspecific for early detection screenings. In the journal Angewandte Chemie, a research team has now introduced a new method that could lead to a significantly more precise and reliable diagnosis. It is based on the selective detection of specific antibodies in blood samples.

Tumours produce certain proteins (tumour-associated antigens) that draw the attention of our constantly “patrolling” immune system and trigger an immune response. As a consequence, antibodies directed against the tumours (tumour-associated autoantibodies) are formed, circulating in the blood at very early stages of the disease – which makes them useful for early detection. An international team led by Roberto Fiammengo and Giovanni Malerba at the University of Verona (Italy) as well as Alfredo Martínez at the Center for Biomedical Research of La Rioja (Logroño, Spain) and Francisco Corzana at the Universidad de La Rioja, has now developed an approach to diagnostic testing for pancreatic cancer that is based on the detection of such special tumour-associated autoantibodies.

They chose to use autoantibodies directed against the tumour-associated form of mucin-1 (TA-MUC1). Mucin-1 is a heavily glycosylated protein (a protein with sugar components) that occurs, for example, in glandular tissue. In many types of tumours, including pancreatic cancer, it is found in significantly elevated concentrations. In addition, the pattern of glycosylation is different from the normal form. The team’s goal was to detect autoantibodies that are directed specifically against TA-MUC1 and are a clear indicator of pancreatic cancer.

Based on structural analyses and computer simulations of known antibodies against TA-MUC1 (SM3 and 5E5), the team designed a collection of synthetic glycopeptides that mimic different segments (epitopes) of TA-MUC1. They also made unnatural modifications to increase the chances of identifying autoantibody subgroups indicative of the disease. The team immobilised these model antigens on gold nanoparticles achieving probes suitable for a serological assay (dot-blot assay). The diagnostic assay was validated with real samples from patients with pancreatic cancer and a healthy control group. Some of the nanoparticle probes could differentiate very well between samples from diseased and healthy individuals demonstrating they detected tumour associated autoantibodies. Notably, these specific autoantibodies displayed significantly better correct positive/false positive ratios than current clinical biomarkers for pancreatic cancer.

Probes with smaller glycopeptide antigens that correspond to only a single epitope, gave better results than larger probes that mimic multiple epitopes – an advantage for easier synthetic production. A short glycopeptide with an unnatural modification to its sugar component was found to be particularly effective for the detection of discriminating autoantibodies. This new structure-based approach could help in the selection of autoantibody subgroups with higher tumour specificity.

Source: Wiley