Category: Cancer

Categories : Cancer GastrointestinalTags :

Scientists Find a Molecule that Promotes Gut Healing and Stifles Tumour Growth

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Researchers at Karolinska Institutet have found a molecule that can both help the intestines to heal after damage and suppress tumour growth in colorectal cancer. The discovery could lead to new treatments for inflammatory bowel disease (IBD) and cancer. The results are published in the journal Nature.

Many patients with inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis do not respond to available treatments, highlighting the need to identify novel therapeutic strategies. In this study, researchers propose that promoting mucosal healing through tissue regeneration could be a valid alternative to immunosuppressive drugs.  

“However, it’s virtually impossible to promote tissue regeneration without the risk of inducing tumour growth, as cancer cells can hijack the body’s natural healing processes and start to grow uncontrollably,” says lead author Srustidhar Das, research specialist in Eduardo Villablanca’s research group at Karolinska Institutet. “We’ve now identified a molecule that can help the intestines to heal after damage while suppressing tumour growth in colorectal cancer.” 

New drug candidates 

In their search for new ways to treat IBD, the researchers have identified a handful of molecules with drug-candidate potential. They found that activation of a protein called the Liver X receptor (LXR) can promote regeneration and suppress tumour growth in colorectal cancer. 

“The discovery of both these functions was astonishing,” says last author Eduardo J. Villablanca, docent at Karolinska Institutet. “We now need to study how LXR controls tumour formation more closely.” 

The researchers used a collection of advanced technologies to conduct their study, which included mapping the transcriptome of intestinal cells. The researchers also cultivated what are known as 3D organoids: small, three-dimensional cell structures that mimic the function and structure of the body’s own organs, albeit in miniature format. 

They then used spatial transcriptomics to map the gene expression in the different tissues, a technique that has been developed at SciLifeLab by scientists from the Royal Institute of Technology (KTH) and Karolinska Institutet in Sweden. 

Third most common cancer 

Patients, the third most common type in Sweden, are often treated with chemotherapy and radiotherapy, but this can cause irritation and swelling of the bowel mucosa with subsequent chronic intestinal inflammation. 

“Thus, this new therapeutic molecule has the potential to treat not only IBD patients but also cancer patients to prevent chronic bowel disorders after radiotherapy and/or chemotherapy,” says Eduardo J. Villablanca. 

Source: Karolinska Institutet

Categories : Cancer VaccinesTags :

Cervical Cancer Deaths in Young Women Plummet after Introduction of HPV Vaccine

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Cervical cancer. Credit: Scientific Animations CC4.0

Cervical cancer deaths have plunged dramatically among women under age 25, and researchers at MUSC Hollings Cancer Center believe this is likely due to HPV vaccination. Their study, published in JAMA, is the first to suggest the impact of HPV vaccination on cervical cancer deaths.

“We observed a substantial reduction in mortality – a 62% drop in cervical cancer deaths over the last decade, likely due to HPV vaccination,” said senior author Ashish Deshmukh, PhD, co-leader of the Cancer Prevention and Control Research Program. “We cannot think of any other reason that would have contributed to such a marked decline.”

The human papillomavirus, or HPV, causes nearly all cases of cervical cancer. The HPV vaccine was introduced in 2006. At first, it was available only to adolescents, but eligibility has since been expanded to include adults up to age 45 in some cases. In South Africa, an HPV vaccination programme started in 2014 for girls in public schools.

Previous studies have looked at the rates of HPV infection, precancer and cervical cancer incidence since the introduction of the vaccine, and all of those indicators have declined. The next logical step was to look at death rates, Deshmukh said.

Although cervical cancer is rare in women under age 25, it does occur. By examining deaths in this age group, researchers were able to see the early impact of the vaccine. Women who were 25 in 2021, the final year included in this study, would have been 10 years old when the vaccine was introduced.

The researchers looked at cervical cancer deaths in three-year blocks of time. Through the 1990s, there were between 50 and 60 cervical cancer deaths nationally in women under the age of 25 in each three-year block of time. During the 2019–2021 time period, there were only 13 deaths.

However, the team sounded an alarm. Healthy People 2030 has a goal of reaching an 80% HPV vaccination rate, but the Centers for Disease Control and Prevention reported earlier this year that only about 60% of 13 to 15 year olds have received the recommended doses.

“There has been a decline in HPV vaccination post COVID-19 in the most recent generation of U.S. adolescents. This is troubling as a decline in vaccination uptake would potentially lead to smaller gains,” Deshmukh said.

Source: Medical University of South Carolina

Categories : Cancer IT in HealthcareTags :

HealthONE Oncology: A New Era in Oncology

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As November highlights prostate cancer awareness, it’s important to remember that cancer is far more than mere statistics. It represents deeply personal journeys marked by uncertainty, fear and hope. With countless people facing a cancer diagnosis in their lifetimes, the call for human-centred and innovative care is more urgent than ever. It is imperative that we support individuals on this challenging journey, ensuring they receive the comprehensive care they deserve.

Leading this transformation is the HealthONE Oncology solution, created by Altron HealthTech in partnership with a leading Oncologist Dr. Ziad Seedat and supported by Dis-Chem Oncology. This innovative solution aims to redefine oncology care by streamlining processes and enhancing the treatment experience for both patients and healthcare providers.  Dr. Ziad Seedat, whose expertise as a dedicated advocate for cancer patients has significantly shaped the design and functionality of the platform. His insights ensure that the technology aligns with the real needs of both patients and healthcare practitioners. This has a positive knock-on impact throughout the healthcare ecosystem.

Timely treatment matters

Timely treatment is essential in the fight against cancer. Unfortunately, the healthcare system can be burdened by extensive approvals and administrative requirements, causing delays that can negatively impact patient outcomes. Research indicates that when cancer care is delayed or inaccessible there is a lower chance of survival, greater problems associated with treatment and higher costs of care.1

The HealthOne Oncology solution addresses these challenges by integrating patients’ medical histories, treatment plans and appointment schedules into one accessible platform.  Dis-Chem Oncology enhances this initiative by working with patients, doctors and medical aids to provide medication and supplies. The tailored support ensures that patients receive medication and support throughout their treatment journey. Their direct oncology pharmacies, providing specialised care and support for cancer patients on‑site at hospitals or private oncology practices, further enhances the value.

Innovative solutions with HealthOne

The HealthOne Oncology solution distinguishes itself through its thoughtful design, developed in consultation with clinicians, including Dr. Seedat. He emphasises the importance of minimising administrative burdens, stating, “Patients should focus on their care, not be overwhelmed by paperwork.” This philosophy is foundational to the platform, which integrates feedback from healthcare providers to address the unique challenges of cancer treatment.

HealthOne Oncology is an integrated electronic health records (EHR) platform that works seamlessly with the HealthOne Practice Management application, saving time and improving productivity. By enabling appointment scheduling, storing existing patient data, automating treatment plans and submitting backlogged claims from a centralised, user-friendly interface, HealthOne empowers practitioners to prioritise patient care. The platform also tracks medical aid authorisations, including treatment expiry dates, helping healthcare providers manage treatment timelines effectively. Standardisation and tracking is crucial; the application monitors every intervention, ensuring that each step in the patient’s journey is documented, including signatures for consent.

Addressing financial challenges

The financial burden of cancer treatment can be overwhelming.  In South Africa treatment costs vary significantly, influenced by factors such as the timing of diagnosis and the specific therapies needed.  Many patients experience substantial financial distress due to medical bills and other cancer associated costs, highlighting the urgent need for effective and affordable solutions to support those facing this challenge. 

The HealthOne Oncology platform aims to standardise workflows and clinical protocols to maintain quality care whilst improving efficiency and reducing costs.

The future of digital health in oncology

Looking ahead, the potential for digital health technologies in oncology is vast. By addressing barriers such as interoperability and complex workflows, the HealthOne Oncology platform aims to create a more cohesive, patient-centred model of care. This partnership between Altron HealthTech, Dis-Chem Oncology and the expertise of Dr Seedat marks a pivotal shift in cancer care, embracing innovation while prioritising patient well-being. In a world where cancer diagnoses are on the rise, the HealthOne Oncology platform is your partner in empowering healthcare providers to deliver exceptional care. Imagine transforming patient experiences, streamlining workflows and significantly reducing costs – all while ensuring that each patient’s journey through cancer is filled with hope, empowerment and improved outcomes.  For medical practitioners eager to elevate their practice and make a meaningful difference in the lives of their patients, adopting this innovative platform is not just a choice; it’s a game changer. Join us in the vital fight against cancer and be part of a brighter, more compassionate future for oncology care.

To read more about Altron HealthTech’s solutions, visit https://eu1.hubs.ly/H0dwmNR0

Sources

  1. Promoting cancer early diagnosis, World Health Organization ↩︎
Categories : Cancer New Compounds and TreatmentsTags :

New Therapy Approach Robs Cancer Cells of their Vital Copper

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© Wiley-VCH, Credit: Angewandte Chemie

While toxic in high concentrations, copper is essential to life as a trace element. Many tumours require significantly more copper than healthy cells for growth – something which new cancer treatments might exploit this. In the journal Angewandte Chemie, a research team from the Max Planck Institute for Polymer Research has now introduced a novel method by which copper is effectively removed from tumours cells, killing them.

Copper is an essential cofactor for a variety of enzymes that play a role in the growth and development of cells. For example, copper ions are involved in antioxidant defence. Cells very strictly regulate the concentration and availability of copper ions. On the one hand, enough copper ions must be on hand; on the other, the concentration of free copper ions in the cytoplasm must be kept very low to avoid undesired side effects. Extracellular, doubly charged copper ions are reduced to singly charged copper, transported into the cell, stored in pools, and transferred to the biomolecules that require them on demand. To maintain the cellular copper equilibrium (homeostasis), cells have developed clever trafficking systems that use a variety of transporters, ligands, chaperones (proteins that help other complex proteins to fold correctly), and co-chaperones.

Because cancer cells grow and multiply much more rapidly, they have a significantly higher need for copper ions. Restricting their access to copper ions could be a new therapeutic approach. The problem is that it has so far not been possible to develop drugs that bind copper ions with sufficient affinity to “take them away” from copper-binding biomolecules.

In cooperation with the Stanford University School of Medicine (Stanford/CA, USA) and Goethe University Frankfurt/Main (Germany), Tanja Weil, Director of the Max Planck Institute for Polymer Research (Mainz) and her team have now successfully developed such a system. At the heart of their system are the copper-binding domains of the chaperone Atox1. The team attached a component to this peptide that promotes its uptake into tumour cells. An additional component ensures that the individual peptide molecules aggregate into nanofibres once they are inside the tumour cells. In this form, the fibre surfaces have many copper-binding sites in the right spatial orientation to be able to grasp copper ions from three sides with thiol groups (chelate complex). The affinity of these nanofibres for copper is so high that they also grab onto copper ions in the presence of copper-binding biomolecules. This drains the copper pools in the cells and deactivates the biomolecules that require copper. As a consequence, the redox equilibrium of the tumour cell is disturbed, leading to an increase in oxidative stress, which kills the tumour cell. In experiments carried out on cell cultures under special conditions, over 85% of a breast cancer cell culture died off after 72 hours while no cytotoxicity was observed for a healthy cell culture.

The research team hopes that some years in the future, these fundamental experiments will perhaps result in the development of useful methods for treating cancer.

Source: Wiley

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 Lab Tests and ImagingTags :

Telltale Chemical in the Breath can Warn of Lung Cancer

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Credit: Scientific Animations CC4.0

Exhaled breath contains chemical clues to what’s going on inside the body, including diseases like lung cancer. And devising ways to sense these compounds could help doctors provide early diagnoses — and improve patients’ prospects. In a study in ACS Sensors, researchers report the development of ultrasensitive, nanoscale sensors that in small-scale tests distinguished a key change in the chemistry of the breath of people with lung cancer.

Besides carbon dioxide, people also exhale other airborne compounds. Researchers have determined that declines in one exhaled chemical — isoprene — can indicate the presence of lung cancer. However, to detect such small shifts, a sensor would need to be highly sensitive, capable of detecting isoprene levels in the parts-per-billion (ppb) range. It would also need to differentiate isoprene from other volatile chemicals and withstand breath’s natural humidity. Previous attempts to engineer gas sensors with characteristics like these have focused on metal oxides, including one particularly promising compound made with indium oxide. A team led by Pingwei Liu and Qingyue Wangset out to refine indium oxide-based sensors to detect isoprene at the level at which it naturally occurs in breath.

The researchers developed a series of indium(III) oxide (In2O3)-based nanoflake sensors. In experiments, they found one type, which they called Pt@InNiOx for the platinum (Pt), indium (In) and nickel (Ni) it contains, performed best. These Pt@InNiOx sensors:

  • Detected isoprene levels as low as 2ppb, a sensitivity that far surpassed earlier sensors.
  • Responded to isoprene more than other volatile compounds commonly found in breath.
  • Performed consistently during nine simulated uses.

More importantly, the authors’ real-time analysis of the nanoflakes’ structure and electrochemical properties revealed that Pt nanoclusters uniformly anchored on the nanoflakes catalyzed the activation of isoprene sensing, leading to the ultrasensitive performance.

Finally, to showcase the potential medical use of these sensors, the researchers incorporated the Pt@InNiOx nanoflakes into a portable sensing device. Into this device they introduced breath collected earlier from 13 people, five of whom had lung cancer. The device detected isoprene levels lower than 40 ppb in samples from participants with cancer and more than 60 ppb from cancer-free participants. This sensing technology could provide a breakthrough in non-invasive lung cancer screening and has the potential to improve outcomes and even save lives, the researchers say.

Source: American Chemical Society

Categories : Cancer ImmunologyTags :

Chronic Activation of the Innate Immune System can Unleash Cancer

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Photo by Sangharsh Lohakare on Unsplash

Along with defending against pathogens, the body’s innate immune system helps to protect the stability of our genomes in unexpected ways that have important implications for the development of cancer, researchers at Memorial Sloan Kettering Cancer Center (MSK) are discovering.

In a pair of recent papers, scientists in the lab of molecular biologist John Petrini, PhD, showed that innate immune signaling plays a key role in maintaining genome stability during DNA replication. Furthermore, the researchers showed that chronic activation of these immune pathways can contribute to tumour development in a mouse model of breast cancer.

Not only do the findings add vital insights to our understanding of fundamental human biology, says Dr Petrini, they may also shed new light on tumour initiation and present potential opportunities for new therapies.

“Living organisms have evolved complex pathways to sense, signal, and repair damaged DNA,” he says. “Here we’re learning new things about the role of the innate immune system in responding to that damage – both in the context of cancer and also in human health more generally.”

How Chronic Activation of the Innate Immune System Can Lead to Cancer

The newest paper, led by first author Hexiao Wang, PhD, a postdoctoral fellow in the Petrini Lab, and published in Genes & Development, reveals a connection between innate immune signaling and tumour development in breast tissue. And, Dr Petrini says, the data suggest that when instability arises in the genome, chronic activation of the innate immune system can greatly increase the chances of developing cancer.

The study focused on a protein complex called the Mre11 complex, which plays a pivotal role in maintaining the stability of the genome by sensing and repairing double-strand breaks in DNA.

To study how problems with the Mre11 complex can lead to cancer, the team manipulated copies of the protein in mammary tissue organoids (miniature lab-grown model organs) and then implanted them into laboratory animals.

When oncogenes (genes known to drive cancer) were activated in these mice, tumors arose about 40% of the time, compared with about 5% in their normal counterparts. And the tumors in the mice with mutant Mre11 organoids were highly aggressive.

The research further showed that the mutant Mre11 led to higher activation of interferon-stimulated genes (ISGs). Interferons are signaling molecules that are released by cells in response to viral infections, immune responses, and other cellular stressors.

They also found that the normally tightly controlled packaging of DNA was improperly accessible in these organoids — making it more likely that genes will get expressed, when they otherwise would be inaccessible for transcription.

“We actually saw differences in the expression of more than 5600 genes between the two different groups of mice,” Dr Petrini says.

And strikingly, these profound effects depended on an immune sensor called IFI205.

When the organoids were further manipulated so they would lack IFI205, the packaging of DNA returned almost to normal, and the mice developed cancer at essentially the same rate as normal mice.

“So what we learned is that problems with Mre11 – which can be inherited or develop during life like other mutations – can create an environment where the activation of an oncogene is much more likely to lead to cancer,” Dr Petrini says. “And that the real lynch pin of this cascade is this innate immune sensor, IFI205, which detects that there’s a problem and starts sending out alarm signals. In other words, when problems with Mre11 occur, chronic activation of this innate immune signaling can significantly contribute to the development of cancer.”

New Understandings Could Pave the Way for Future Treatments

The work builds on a previous study, led by Christopher Wardlaw, PhD, a former senior scientist in the Petrini Lab, that appeared in Nature Communications.

That study focused on the role of the Mre11 complex in maintaining genomic integrity. It found that when the Mre11 complex is inactive or deficient, it results in the accumulation of DNA in the cytoplasm of cells and in the activation of innate immune signaling. This research primarily looked at the involvement of ISG15, a protein made by an interferon-stimulating gene, in protecting against replication stress and promoting genomic stability.

“Together, these studies shed new light on how the Mre11 complex works to protect the genome when cells replicate, and how, when it’s not working properly, it can trigger the innate immune system in ways that can promote cancer,” D. Petrini says.

By shedding light on the interrelationships between these complex systems and processes, the researchers hope to identify new strategies to prevent or treat cancer, he adds, such as finding ways to short-circuit the increased DNA accessibility when Mre11 isn’t working properly.

Source: Memorial Sloan Kettering Cancer Center

Categories : Cancer NeurologyTags :

Early Radiotherapy Treatment of Vestibular Schwannomas Prevents Problems

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Photo by National Cancer Institute on Unsplash

Patients with a small cranial nerve tumour that can cause hearing loss, vertigo, imbalance and ringing in the ears have typically been watched rather than proactively treated, as the risks of early intervention were thought to outweigh the benefits. Now a study shows that even those patients benefit significantly from non-invasive stereotactic radiosurgery, led by UVA Health physicians has found. The findings were reported in Neurosurgery.

Doctors typically treat larger forms of the tumours, called vestibular schwannomas, while taking a “watch and wait” approach to smaller tumours that aren’t causing appreciable problems. But the new research, from UVA Health neurosurgeon Jason Sheehan, MD, PhD, and collaborators, could change how asymptomatic schwannomas are managed. Their findings demonstrated that stereotactic radiosurgery – a highly targeted form of radiation therapy – can prevent small tumours from growing over time while at the same time sparing patients from potentially irreversible problems in the future.

“This study and our recent Vestibular Schwannoma International Study of Active Surveillance versus Stereotactic Radiosurgery [VISAS] trial demonstrate that radiosurgery affords effective and durable tumour control while more often avoiding the neurological complications that come from watching a vestibular schwannoma,” Sheehan said. “Over time, Gamma Knife radiosurgery bends the curve of growth and problems that commonly arise from watching even the smallest of vestibular schwannomas.”

About vestibular schwannomas

Vestibular schwannomas are growths on a cranial nerve that connects the brain and inner ear. This nerve transmits information about head movements, helps us control our balance and allows us to hear. The growths, however, can disrupt the nerve’s important functions, causing hearing loss, unsteadiness, headaches, tinnitus (ringing in the ear), facial numbness/paralysis and other problems. 

Seeking to improve care for patients with these tumours, Sheehan and his team performed a trial through the International Radiosurgery Research Foundation looking at 261 adults with the smallest category of vestibular schwannomas. These were usually picked up early, and the patients often were high functioning and had the most to lose from tumour growth over time. Of the study participants, 182 received stereotactic radiosurgery, while 79 did not. 

The patients who underwent radiosurgery using the Gamma Knife system showed consistently better tumour control over time. In this group, 99% of the patients’ tumours either stayed the same size, grew very little (less than 25%) or shrank. This was true at 3 years, 5 years, and 8 years. Only one patient’s tumour significantly increased in size.

Tumour control was much worse among those who didn’t receive radiosurgery: 37% saw their tumours grow significantly at 3 years, 50% at five years, and 67% at eight years.

That difference was seen plainly in the symptoms the patients experienced. Radiosurgery was associated with a 54% lower rate of tinnitus, a 51% lower rate of cranial nerve deterioration and an 83% lower rate of vestibular dysfunction that causes dizziness and loss of balance. 

Even with Gamma Knife radiosurgery to treat the tumour arising from this very delicate neural structure, hearing was preserved similarly in both groups.

Sheehan, an expert in stereotactic radiosurgery and brain tumours, urges physicians to take note of the findings because tumour symptoms are often irreversible as the tumour grows. Acting early, before symptoms develop, could greatly improve patients’ long-term quality of life, he says.

“In brain surgery, particularly involving the hearing and balance nerve, our approach must be exceedingly refined,” he said. “This study shows that Gamma Knife radiosurgery substantially improves the future trajectory of vestibular schwannoma patients.”

Source: University of Virginia Health System

Categories : Cancer NeurologyTags :

A Way to Make Glioblastoma Cells Visible to Immune Cells

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MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

Patients with glioblastoma typically survive less than two years after diagnosis, even with cutting-edge therapies. The latest immunotherapies have been unsuccessful, likely because glioblastoma cells have few, if any, natural targets for the immune system to attack.

In a cell-based study, scientists at Washington University School of Medicine have forced glioblastoma cells to display immune system targets, potentially making them visible to immune cells and newly vulnerable to immunotherapies. The strategy involves a combination of two drugs, each already FDA-approved to treat different cancers.

The study is online in the journal Nature Genetics.

“For patients whose tumours do not naturally produce targets for immunotherapy, we showed there is a way to induce their generation,” said co-senior author Ting Wang, PhD, professor of medicine and Department of Genetics head at WashU Medicine. “In other words, when there is no target, we can create one. This is a very new way of designing targeted and precision therapies for cancer. We are hopeful that in the near future we will be able to move into clinical trials, where immunotherapy can be combined with this strategy to provide new therapeutic approaches for patients with very hard-to-treat cancers.”

To create immune targets on cancer cells, Wang has focused on stretches of DNA in the genome known as transposable elements. In recent years, transposable elements have emerged as a double-edged sword in cancer, according to Wang. His work has shown that transposable elements play a role in causing tumours to develop even as they present vulnerabilities that could be exploited to create new cancer treatment strategies.

For this study, Wang’s team took advantage of the fact that transposable elements naturally can cause a tumour to churn out random proteins that are unique to the tumour and not present in normal cells. Called tumour antigens or neoantigens, these unusual proteins could be the targets for immunotherapies, such as checkpoint inhibitors, antibodies, vaccines and genetically engineered T cell therapies.

Even so, some tumours, including glioblastoma, have few immune targets produced naturally by transposable elements. To address this, Wang and his colleagues, including co-senior author Albert H. Kim, MD, PhD, neurosurgery professor, have demonstrated how to purposely force transposable elements to produce immune system targets on glioblastoma cells that normally lack them.

The researchers used a combination of two drugs that influence the epigenome, which controls gene activation. When treated with the two epigenetic therapy drugs, the tightly packed DNA molecules of the glioblastoma cells unfurled, triggering transposable elements to begin making the unusual proteins that could be used to target the cancer cells. The two drugs were decitabine, which is approved to treat myelodysplastic syndromes, a group of blood cancers; and panobinostat, which is approved for multiple myeloma, a cancer of white blood cells.

Before investigating this strategy in people, the researchers are seeking ways to target the epigenetic therapy so that only the tumour cells are induced to make neoantigens. In the new study, the researchers cautioned that normal cells also produced targets when exposed to the two drugs. Even though normal cells didn’t produce as many neoantigens as the glioblastoma cells did, Wang and Kim said there is a risk of unwanted side effects if normal cells create these targets as well.

In ongoing work, Wang and Kim are investigating how to use CRISPR molecular editing technology to induce specific parts of the genome in cancer cells to produce the same neoantigens from transposable elements that are common across the human population. Such a strategy could give many patients’ tumours – even different cancer types – the same targets that could respond to the same immunotherapy, while sparing healthy cells. There are then multiple possible ways to go after such a shared target, including checkpoint inhibitors, vaccines, engineered antibodies and engineered T cells.

Source: Washington University School of Medicine

Categories : CancerTags :

An Unexpected Effect Unlocks New Treatment Option for Prostate Cancer

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Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

An international research team led by MedUni Vienna may have found a new cancer treatment strategy – by activating a pathway which normally promotes cancer. Unexpectedly, this turned out to not only slow tumour growth, but also stimulates the immune system to combat tumour cells. The results of the study have just been published in Molecular Cancer.

The scientific team focused its investigations on the GP130 signalling pathway, which researchers expect to have a major potential in the fight against cancer. The signalling pathway, which is mediated by the protein GP130, plays a central role in cell communication and influences the activity of the transcription factor STAT3, which in turn is associated with the development and spread of tumours. Accordingly, blocking the GP130 signalling pathway is currently seen as a great hope in cancer medicine. Yet the current study proves the opposite: tumour growth can be slowed down not by inhibiting but by activating the GP130 signalling pathway in prostate cells.
 
New hope, especially for aggressive tumours

To achieve these new findings, the researchers investigated genetically modified mice in which GP130 was specifically activated in the prostate. “This allowed us to directly observe the reduction in tumour growth in the cell,” reports Lukas Kenner (Clinical Department of Pathology, MedUni Vienna), who led the study together with Stefan Rose-John (Biochemical Institute, University of Kiel). The results were further backed up by analyses of tissue samples from prostate cancer patients. This showed that high GP130 values correlate with a better survival rate. At the same time, extensive molecular analyses were carried out, including gene expression profiling.

“Our research provides exciting new evidence that the activation of GP130 in prostate cells not only slows tumour growth, but also stimulates the immune system to actively fight the cancer cells,” says Lukas Kenner, summarising the significance of the results, which will now be confirmed in further studies. The research work opens up a promising new therapeutic option, particularly for aggressive prostate cancer, which is still difficult to treat.

Source: Medical University of Vienna