Tag: cancer treatment

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A Citrus Remedy Quenches Dry Mouth in Cancer Patients

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Photo by Diana Polekhina on Unsplash

A natural citrus oil from oranges, lemons, and limes is proving highly effective in relieving dry mouth, and when combined with a new lipid formulation, new research suggests it may be effective without significant side effects.

Developed by the University of South Australia in collaboration with the Medical School at Stanford University, this world first formulation uniquely combines limonene (a citrus essential oil) with a lipid-based drug delivery system to treat dry mouth (xerostomia), a common side effect of radiotherapy.

The new formula demonstrated 180-fold better solubility than pure limonene in lab experiments and boosted relative bioavailability by over 4000% compared to pure limonene in pre-clinical trials.

Dry mouth is the most reported side effect following radiotherapy for the treatment of head and neck cancer, affecting up to 70% of patients due to salivary gland damage. It can lead to difficulty speaking and swallowing, significantly reducing quality of life.

Limonene has protective effects on saliva production during radiotherapy, but its poor solubility means high doses are needed to take effect, and these cause indigestion, abdominal discomfort and unpleasant ‘citrus burps’.

Lead researcher, Professor Clive Prestidge says UniSA’s new limonene-lipid combination creates a ‘super-solubilising’ treatment that reduces dry mouth at lower dose and without uncomfortable side effects.

“The therapeutic benefits of limonene are well known. It’s used as an anti-inflammatory, antioxidant, and mood-enhancing agent, and can also improve digestion and gut function. But despite its widespread use, its volatility and poor solubility have limited its development as an oral therapy,” Prof Prestidge says.

“As limonene is an oil, it forms a film on the top of the stomach contents, causing significant stomach pain and discomfort.

“Our novel formulation combines limonene with healthy fats and oils – called lipids – to create a super-solubilising compound that the body can easily absorb with reduced uncomfortable side effects.

“This increases the dispersion of limonene in the stomach, boosts absorption, and controls biodistribution – all while increasing a patient’s saliva production and reducing dry mouth.”

Co-researcher Dr Leah Wright says the formulation has the potential to significantly improve the quality of life for cancer patients and others suffering dry mouth conditions.

“Cancer patients undergoing radiotherapy and other medical treatments regularly experience dry mouth, which not only prevents them from comfortably swallowing, but can also have other negative and potentially life-threatening outcomes,” Dr Wright says. 

“While limonene can be ingested directly, it’s not well tolerated, especially by those with dry mouth. Plus, its poor absorption prevents it from effectively reaching the salivary glands – the target site.

“This inventive and highly impactful limonene-lipid formulation could provide a simple, effective oral solution for dry mouth, offering cancer patients long-lasting relief and comfort, improved oral health, and a higher quality of life during a difficult time.”

Clinical trials for the new formula are ongoing, with next steps to be announced soon.

Source: University of South Australia

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How to Stop Melanoma’s Incredibly Swift Evasion of Treatment

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Melanoma Cells. Credit: National Cancer Institute

Researchers have uncovered a stealth survival strategy that melanoma cells use to evade targeted therapy, offering a promising new approach to improving treatment outcomes.

The study, published in Cell Systems and conducted by researchers at the Institute for Systems Biology (ISB) and Massachusetts Institute of Technology (MIT) identifies a non-genetic, reversible adaptation mechanism that allows melanoma cells to survive treatment with BRAF inhibitors. By identifying and blocking this early response, researchers proposed a combination therapy that could delay resistance and enhance the effectiveness of existing treatments.

Cracking the Code of Melanoma’s Drug Escape

Melanoma, the deadliest form of skin cancer, is often driven by mutations in the BRAF gene, which fuels uncontrolled tumor growth. While BRAF inhibitors (such as vemurafenib) initially halt tumor growth, many tumors quickly adapt and survive treatment, leading to therapy failure.

Unlike traditional resistance driven by genetic mutations, this study uncovers an early, dynamic adaptation process that occurs within hours to days of drug treatment – long before genetic resistance takes hold. Surprisingly, this process does not rely on reactivating the BRAF-ERK pathway, which is the usual resistance mechanism.

Using cutting-edge mass spectrometry-based phosphoproteomics and deep transcriptomics analyses, researchers mapped the molecular shifts in melanoma cells over minutes, hours, and days of BRAF inhibitor treatment.

“We found that while the BRAF-ERK signaling pathway was quickly and durably suppressed, cancer cells did not rely on reactivating ERK to survive. Instead, they triggered an alternative SRC family kinase (SFK) signaling pathway, which promoted cell survival and eventual recovery,” said Chunmei Liu, PhD, a bioinformatics scientist at ISB and co-first author of the paper.

Turning a Weakness Into a Target

A key discovery in this study came when researchers linked SFK activation to reactive oxygen species (ROS), a cellular stress response that builds up under BRAF inhibition. As ROS levels surged, SFK activity spiked, helping melanoma cells withstand treatment. However, this adaptation was reversible – when treatment was removed, cells returned to their original state.

Recognizing this Achilles’ heel, the team tested a combination approach: pairing BRAF inhibitors with the SFK inhibitor dasatinib.

“By adding dasatinib, we blocked this adaptive escape mechanism, significantly reducing melanoma cell survival and stabilising tumours in animal models,” said ISB Associate Professor Wei Wei, PhD, co-corresponding author.

Importantly, SFK inhibition alone had little effect on melanoma cells, highlighting the need for a strategic combination therapy to suppress melanoma adaptation before resistance fully develops. 

“This approach has the potential to prolong the effectiveness of BRAF inhibitors and improve patient outcomes,” said ISB President and Professor Jim Heath, PhD, co-corresponding author.

Looking Ahead: A Path to the Clinic

Beyond uncovering a key mechanism of drug adaptation, this research underscores the importance of early intervention to prevent it from happening. It also highlights ROS accumulation and SFK activation as potential biomarkers for identifying patients who may benefit from this combination therapy.

Further preclinical studies and clinical trials will be necessary to validate this combination therapy strategy and determine its potential for broader clinical use.

Source: Institute for Systems Biology

Categories : CancerTags :

Scientists Upend the Current Understanding of How PARP Inhibitors Kill Cancer

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Breast cancer cells. Image by National Cancer Institute

Research by UMass Chan Medical School scientists poses a new explanation for how PARP inhibitor drugs attack and destroy BRCA1 and BRCA2 tumour cells. Published in Nature Cancer, this study illustrates how a small DNA nick – a break in one strand of the DNA – can expand into a large single-stranded DNA gap, killing BRCA mutant cancer cells, including drug-resistant breast cancer cells. These findings identify a novel vulnerability that may be a potential target for new therapeutics. 

Mutations in BRCA1 and BRCA2, tumour suppressor genes that play a crucial role in DNA repair, substantially increase the likelihood of cancer. These cancers are, however, quite sensitive to anticancer drugs such as poly (ADP-ribose) polymerase inhibitors (PARPi). When successful, these cancer treatments cause enough DNA damage to trigger cancer cell death. However, the array of different damages potentially induced by these drugs makes it difficult to pinpoint the exact cause of cell death. Additionally, PARPi resistance does occur, complicating treatment and leading to recurrent cancer.

“The conventional thinking has been that single-stranded DNA breaks from PARPi ultimately generated DNA double-strand breaks, and that was what was killing the BRCA mutant cancer cells,” said Sharon Cantor, PhD, professor of molecular, cell and cancer biology. “Yet, there wasn’t much in the literature that experimentally confirmed this belief. We decided to go back to the beginning and use genome engineering tools to see how these cells dealt with single-strand nicks to their DNA.” 

Using CRISPR technology, Cantor and Jenna M. Whalen, PhD, a postdoctoral researcher in the Cantor lab, introduced small, single strand breaks into several breast cancer cell lines, such as those with the BRCA1 and BRCA2 mutation, as well BRCA-proficient cells. They found that cells with BRCA1 or BRCA2 deficiency were uniquely sensitive to nicks. They also found that breast cancer cells that lose components of the complex that protects DNA from unnecessary DNA end cuts become resistant to chemotherapy drugs such as PARP inhibitors. However, restoring double strand DNA repair functions in breast cancer cells did not save the cells from dying, thus demonstrating that these repair functions are not critical for breast cancer cell survival. Instead, the cells become even more sensitive to single strand nicks, which then accumulate and form large gaps.  

“Our findings reveal that it is the resection of a nick into a single-stranded DNA gap that drives this cellular lethality,” said Whalen. “This highlights a distinct mechanism of cytotoxicity, where excessive resection, rather than failed DNA repair by homologous recombination, underpins the vulnerability of BRCA-deficient cells to nick-induced damage.” 

The findings suggest that PARPi may also work by generating nicks in BRCA1 and BRCA2 cancer cells, exploiting their inability to effectively process these lesions. For cancers that have developed PARPi-resistance, nick-inducing therapies provide a promising mechanism to bypass resistance and selectively target resection-dependent vulnerabilities.  

“Importantly, our findings suggest a path forward for treating PARPi-resistant cells that regained homologous recombination repair: to kill these cells, nicks could be induced such as through ionizing radiation,” said Cantor. “By targeting nicks in this way, therapies could effectively exploit the persistent vulnerabilities of these resistant cancer cells.”

Source: UMass Chan Medical School

Categories : Cancer IT in HealthcareTags :

AI Boosts Efficacy of Cancer Treatment, but Doctors Remain Key

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Photo by Tara Winstead on Pexels

A new study led by researchers from Moffitt Cancer Center, in collaboration with investigators from the University of Michigan,  shows that artificial intelligence (AI) can help doctors make better decisions when treating cancer. However, it also highlights challenges in how doctors and AI work together. The study, published in Nature Communications, focused on AI-assisted radiotherapy for non-small cell lung cancer and hepatocellular carcinoma.

Radiotherapy is a common treatment for cancer that uses high-energy radiation to kill or shrink tumors. The study looked at a treatment approach known as knowledge-based response-adaptive radiotherapy (KBR-ART). This method uses AI to optimize treatment outcomes by suggesting treatment adjustments based on how well the patient responds to the therapy.

The study found that when doctors used AI to help decide the best treatment plan, they made more consistent choices, reducing differences between doctors’ decisions. However, the technology didn’t always change doctors’ minds. In some cases, doctors disagreed with the AI suggested and made treatment decisions based on their experience and patient needs.

Doctors were asked to make treatment decisions for cancer patients, first without any technological assistance, and then with the help of AI. The AI system developed by the researchers uses patient data like medical imaging and test results to recommend changes in radiation doses. While some doctors found the suggestions helpful, others preferred to rely on their own judgment.

“While AI offers insights based on complex data, the human touch remains crucial in cancer care,” said Moffitt’s Issam El Naqa, PhD. “Every patient is unique, and doctors must make decisions based on both AI recommendations and their own clinical judgment.”

The researchers noted that while AI can be a helpful tool, doctors need to trust it for it to work well. Their study found that doctors were more likely to follow AI suggestions when they felt confident in its recommendations. “Our research shows that AI can be a powerful tool for doctors,” said Dipesh Niraula, PhD, an applied research scientist in Moffitt’s Machine Learning Department. “But it’s important to recognise that AI works best when it’s used as a support, not a replacement, for human expertise. Doctors bring their expertise and experience to the table, while AI provides data-driven insights. Together, they can make better treatment plans, but it requires trust and clear communication.”

The study’s authors hope that their findings can lead to better integration of AI tools and collaborative relationships that doctors can use to make more personalised treatment decisions for cancer patients. They also plan to further investigate how AI can support doctors in other medical fields.

Source: H. Lee Moffitt Cancer Center & Research Institute

Categories : Cancer COVIDTags :

COVID Caused Cancer Tumours to Shrink in Mice – New Study

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SARS-CoV-2 infecting a human cell. Credit: NIH

Justin Stebbing, Anglia Ruskin University

A fascinating new study, published in the Journal of Clinical Investigation, has revealed an unexpected potential benefit of severe COVID infection: it may help shrink cancer.

This surprising finding, based on research conducted in mice, opens up new possibilities for cancer treatment and sheds light on the complex interactions between the immune system and cancer cells – but it certainly doesn’t mean people should actively try to catch COVID.

The data outlining the importance of the immune system in cancer is considerable and many drugs target the immune system, unlocking its potential, an important focus of my own research.

The study here focused on a type of white blood cell called monocytes. These immune cells play a crucial role in the body’s defence against infections and other threats. However, in cancer patients, monocytes can sometimes be hijacked by tumour cells and transformed into cancer-friendly cells that protect the tumour from the immune system.

What the researchers discovered was that severe COVID infection causes the body to produce a special type of monocyte with unique anti-cancer properties. These “induced” monocytes are specifically trained to target the virus, but they also retain the ability to fight cancer cells.

To understand how this works, we need to look at the genetic material of the virus that causes COVID. The researchers found that these induced monocytes have a special receptor that binds well to a specific sequence of COVID RNA. Ankit Bharat, one of the scientists involved in this work from Northwestern University in Chicago explained this relationship using a lock-and-key analogy: “If the monocyte was a lock, and the COVID RNA was a key, then COVID RNA is the perfect fit.”

Remarkable

To test their theory, the research team conducted experiments on mice with various types of advanced (stage 4) cancers, including melanoma, lung, breast and colon cancer. They gave the mice a drug that mimicked the immune response to a severe COVID infection, inducing the production of these special monocytes. The results were remarkable. The tumours in the mice began to shrink across all four types of cancer studied.

Unlike regular monocytes, which can be converted by tumours into protective cells, these induced monocytes retained their cancer-fighting properties. They were able to migrate to the tumour sites – a feat that most immune cells cannot accomplish – and, once there, they activated natural killer cells. These killer cells then attacked the cancer cells, causing the tumours to shrink.

This mechanism is particularly exciting because it offers a new approach to fighting cancer that doesn’t rely on T cells, which are the focus of many current immunotherapy treatments.

While immunotherapy has shown promise, it only works in about 20% to 40% of cases, often failing when the body can’t produce enough functioning T cells. Indeed it’s thought that the reliance on T cell immunity is a major limitation of current immunotherapy approaches.

This new mechanism, by contrast, offers a way to selectively kill tumours that is independent of T cells, potentially providing a solution for patients who don’t respond to traditional immunotherapy.

It’s important to note that this study was conducted in mice, and clinical trials will be necessary to determine if the same effect occurs in humans.

Maybe aspects of this mechanism could work in humans and against other types of cancer as well, as it disrupts a common pathway that most cancers use to spread throughout the body.

While COVID vaccines are unlikely to trigger this mechanism (as they don’t use the full RNA sequence as the virus), this research opens up possibilities for developing new drugs and vaccines that could stimulate the production of these cancer-fighting monocytes.

Few would have imagined that there’d be an upside to COVID. Photo by Kelly Sikkema on Unsplash

Trained immunity

The implications of this study extend beyond COVID and cancer. It shows how our immune system can be trained by one type of threat to become more effective against another. This concept, known as “trained immunity”, is an exciting area of research that could lead to new approaches for treating a wide range of diseases.

However, it’s crucial again to emphasise that this doesn’t mean people should seek out COVID infection as a way to fight cancer, and this is especially dangerous as I have described. Severe COVID can be life-threatening and has many serious long-term health consequences.

Instead, this research provides valuable insights that could lead to the development of safer, more targeted treatments in the future. As we continue to grapple with the aftermath of the COVID pandemic, new infections and long COVID, studies like this remind us of the importance of basic scientific research.

Even in the face of a global health crisis, researchers are finding ways to advance our understanding of human biology and disease. This work not only helps us combat the immediate threat of COVID, but also paves the way for breakthroughs in treating other serious conditions such as cancer.

While there’s still much work to be done before these findings can be translated into treatments for human patients, this study represents an exciting step forward in our understanding of the complex relationship between viruses, the immune system and cancer. It offers hope for new therapeutic approaches and underscores the often unexpected ways in which scientific discoveries can lead to medical breakthroughs.

Justin Stebbing, Professor of Biomedical Sciences, Anglia Ruskin University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : CancerTags :

Rare Disease Sheds Light on a Side Effect of Immunotherapy

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

A multinational collaboration co-led by the Garvan Institute of Medical Research has uncovered a potential explanation for why some cancer patients receiving a type of immunotherapy called checkpoint inhibitors experience increased susceptibility to common infections.

The findings, published in the journal Immunity, provide new insights into immune responses and reveal a potential approach to preventing the common cancer therapy side effect.

“Immune checkpoint inhibitor therapies have revolutionised cancer treatment by allowing T cells to attack tumours and cancer cells more effectively. But this hasn’t been without side effects – one of which is that approximately 20% of cancer patients undergoing checkpoint inhibitor treatment experience an increased incidence of infections, a phenomenon that was previously poorly understood,” says Professor Stuart Tangye, co-senior author of the study and Head of the Immunology and Immunodeficiency Lab at Garvan.

“Our findings indicate that while checkpoint inhibitors boost anti-cancer immunity, they can also handicap B cells, which are the cells of the immune system that produce antibodies to protect against common infections. This understanding is a critical first step in understanding and reducing the side effects of this cancer treatment on immunity.”

Insights to improve immunotherapy

The researchers focused on the molecule PD-1, which acts as a ‘handbrake’ on the immune system, preventing overactivation of T cells. Checkpoint inhibitor therapies work by releasing this molecular ‘handbrake’ to enhance the immune system’s ability to fight cancer.

The study, which was conducted in collaboration with Rockefeller University in the USA and Kyoto University Graduate School of Medicine in Japan, examined the immune cells of patients with rare cases of genetic deficiency of PD-1, or its binding partner PD-L1, as well as animal models lacking PD-1 signalling. The researchers found that impaired or absent PD-1 activity can significantly reduce the diversity and quality of antibodies produced by memory B cells – the long-lived immune cells that ‘remember’ past infections.

“We found that people born with a deficiency in PD-1 or PD-L1 have reduced diversity in their antibodies and fewer memory B cells, which made it harder to generate high-quality antibodies against common pathogens such as viruses and bacteria,” says Dr Masato Ogishi, first author of the study, from Rockefeller University.

Professor Tangye adds: “This dampening of the generation and quality of memory B cells could explain the increased rates of infection reported in patients with cancer receiving checkpoint inhibitor therapy.”

Co-author Dr Kenji Chamoto, from Kyoto University, says, “PD-1 inhibition has a ‘yin and yang’ nature: it activates anti-tumour immunity but at the same time impedes B-cell immunity. And this duality seems to stem from a conserved mechanism of immune homeostasis.”

New recommendation for clinicians

The researchers say the findings highlight the need for clinicians to monitor B cell function in patients receiving checkpoint inhibitors and point to preventative interventions for those at higher risk of infections.

Co-senior author Dr Stéphanie Boisson-Dupuis, from Rockefeller University, says, “Although PD-1 inhibitors have greatly improved cancer care, our findings indicate that clinicians need to be aware of the potential trade-off between enhanced anti-tumour immunity and impaired antibody-mediated immunity.”

“One potential preventative solution is immunoglobulin replacement therapy (IgRT), an existing treatment used to replace missing antibodies in patients with immunodeficiencies, which could be considered as a preventative measure for cancer patients at higher risk of infections,” she says.

From rare cases to insights to benefit all

 “Studying cases of rare genetic conditions such as PD-1 or PD-L1 deficiency enables us to gain profound insights into how the human immune system normally works, and how our own manipulation of it can affect it. Thanks to these patients, we’ve found an avenue for fine-tuning cancer immunotherapies to maximise benefit while minimising harm,” says Professor Tangye.

Looking ahead, the researchers will explore ways to refine checkpoint inhibitor treatments to maintain their powerful anti-cancer effects while preserving the immune system’s ability to fight infections.

“This research highlights the potential for cancer, genomics and immunology research to inform one another, enabling discoveries that can benefit the broader population,” says Professor Tangye.

Professor Stuart Tangye is a Conjoint Professor at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney.

Source: Garvan Institute of Medical Research

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 : Cancer New Compounds and TreatmentsTags :

New Anti-cancer Agent Works Without Oxygen

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Human colon cancer cells. Credit: National Cancer Institute

Tumours often contain areas of oxygen-deficient tissue that frequently withstand conventional therapies. This is because the drugs applied in tumours require oxygen to be effective. An international research team has developed a novel mechanism of action that works without oxygen: polymeric incorporated nanocatalysts target the tumour tissue selectively and switch off the glutathione that the cells need to survive. The team published their findings in the journal Nature Communications.

Why tumours shrink but don’t disappear

Study leader Dr Johannes Karges from Ruhr University Bochum, Germany, explained: “As tumours grow very quickly, consume a lot of oxygen and their vascular growth can’t necessarily keep pace, they often contain areas that are poorly supplied with oxygen.” These areas, often in the centre of the tumour, frequently survive treatment with conventional drugs, so that the tumour initially shrinks but doesn’t disappear completely. This is because the therapeutic agents require oxygen to be effective. 

The mechanism of action developed by Karges’ team works without oxygen. “It’s a catalyst based on the element ruthenium, which oxidises the naturally present glutathione in the cancer cells and switches it off,” explains Karges. Glutathione is essential for the survival of cells and protects them from a wide range of different factors. If it ceases to be effective, the cell deteriorates. 

Compound accumulates in tumour tissue

All cells of the body need and contain glutathione. However, the catalyst has a selective effect on cancer cells as it is packaged in polymeric nanoparticles that accumulate specifically in the tumour tissue. Experiments on cancer cells and on mice with human tumours, that were considered incurable, proved successful. “These are encouraging results that need to be confirmed in further studies,” concludes Johannes Karges. “Still, there’s a lot of research work to be done before it can be used in humans.”

Source: Ruhr-University Bochum

Categories : Cancer New Compounds and TreatmentsTags :

Crop-destroying Fungus Yields a Potential Colorectal Cancer Treatment

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Plant fungus provides new drug with a new cellular target

Human colon cancer cells. Credit: National Cancer Institute

Novel chemical compounds from a fungus could provide new perspectives for treating colorectal cancer, one of the most common and deadliest cancers worldwide. The fungus, Bipolaris victoriae, is otherwise known as a fungal plant pathogen which in the 1940s caused the “Victoria blight”, decimating oats and similar grains in the US.

In the journal Angewandte Chemie, researchers reported on the isolation and characterisation of a previously unknown class of metabolites (terpene-nonadride heterodimers). One of these compounds effectively kills colorectal cancer cells by attacking the enzyme DCTPP1, which thus may serve as a potential biomarker for colorectal cancer and a therapeutic target.

Rather than using conventional cytostatic drugs, which have many side effects, modern cancer treatment frequently involves targeted tumour therapies directed at specific target molecules in the tumour cells. The prognosis for colorectal cancer patients remains grim however, demanding new targets and novel drugs.

Targeted tumour therapies are mostly based on small molecules from plants, fungi, bacteria, and marine organisms. About half of current cancer medications were developed from natural substances. A team led by Ninghua Tan, Yi Ma, and Zhe Wang at the China Pharmaceutical University (Nanjing, China) chose to use Bipolaris victoriae S27, a fungus that lives on plants, as the starting point in their search for new drugs.

The team first analysed metabolic products by cultivating the fungus under many different conditions (OSMAC method, one strain, many compounds). They discovered twelve unusual chemical structures belonging to a previously unknown class of compounds: terpene-nonadride heterodimers, molecules made from one terpene and one nonadride unit. Widely found in nature, terpenes are a large group of compounds with very varied carbon frameworks based on isoprene units. Nonadrides are nine-membered carbon rings with maleic anhydride groups. The monomers making up this class of dimers termed “bipoterprides” were also identified and were found to contain additional structural novelties (bicyclic 5/6-nonadrides with carbon rearrangements).

Nine of the bipoterprides were effective against colorectal cancer cells. The most effective was bipoterpride No. 2, which killed tumour cells as effectively as the classic cytostatic drug Cisplatin. In mouse models, it caused tumours to shrink with no toxic side effects.

The team used a variety of methods to analyse the drug’s mechanism: bipoterpride 2 inhibits dCTP-pyrophosphatase 1 (DCTPP1), an enzyme that regulates the cellular nucleotide pool. The heterodimer binds significantly more tightly than each of its individual monomers. The activity of DCTPP1 is elevated in certain types of tumours, promoting the invasion, migration, and proliferation of the cancer cells while also inhibiting programmed cell death. It can also help cancer cells to resist treatment. Bipoterpride 2 inhibits this enzymatic activity and disrupts the now pathologically altered amino acid metabolism in the tumour cells.

The team was thus able to identify DCTPP1 as a new target for the treatment of colorectal cancer and bipoterprides as new potential drug candidates.

Source: Wiley