Tag: chemotherapy

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Zapping Glioblastoma With Electric Fields Slows Tumour Growth

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A new study led by Keck Medicine of USC researchers may have uncovered an effective combination therapy for glioblastoma, a brain tumour diagnosis with few available effective treatments. According to the National Brain Tumor Society, the average survival for patients diagnosed with glioblastoma is eight months.

The study, which was published in the journal Med, finds that using Tumour Treating Fields therapy (TTFields), which delivers targeted waves of electric fields directly into tumours to stop their growth and signal the body’s immune system to attack cancerous tumour cells, may extend survival among patients with glioblastoma, when combined with immunotherapy (pembrolizumab) and chemotherapy (temozolomide).

TTFields disrupt tumour growth using low-intensity, alternating electric fields that push and pull key structures inside tumour cells in continually shifting directions, making it difficult for the cells to multiply. Preventing tumour growth gives patients a better chance of successfully fighting the cancer. When used to treat glioblastoma, TTFields are delivered through a set of mesh electrodes that are strategically positioned on the scalp, generating fields at a precise frequency and intensity focused on the tumour. Patients wear the electrodes for approximately 18 hours a day.

Researchers observed that TTFields attract more tumour-fighting T cells, which are white blood cells that identify and attack cancer cells, into and around the glioblastoma. When followed by immunotherapy, these T cells stay active longer and are replaced by even stronger, more effective tumour-fighting T cells.

“By using TTFields with immunotherapy, we prime the body to mount an attack on the cancer, which enables the immunotherapy to have a meaningful effect in ways that it could not before,” said David Tran, MD, PhD, chief of neuro-oncology with Keck Medicine, co-director of the USC Brain Tumor Center and corresponding author of the study. “Our findings suggest that TTFields may be the key to unlocking the value of immunotherapy in treating glioblastoma.”

TTFields are often combined with chemotherapy in cancer treatment. However, even with aggressive treatment, the prognosis for glioblastoma remains poor. Immunotherapy, while successful in many other cancer types, has also not proved effective for glioblastoma when used on its own.

However, in this study, adding immunotherapy to TTFields and chemotherapy was associated with a 70% increase in overall survival. Notably, patients with larger, unresected (not surgically removed) tumours showed an even stronger immune response to TTFields and lived even longer. This suggests that, when it comes to kick-starting the body’s immune response against the cancer, having a larger tumour may provide more targets for the therapy to work against.

Using alternating electric fields to unlock immunotherapy

Pembrolizumab, the immunotherapy used in this study, is an immune checkpoint inhibitor (ICI), which enhances the body’s natural ability to fight cancers by improving T cells’ ability to identify and attack cancer cells.

However, there are typically few T cells in and around glioblastomas because these tumours originate in the brain and are shielded from the body’s natural immune response by the blood-brain barrier. This barrier safeguards the brain by tightly regulating which cells and substances enter from the bloodstream. Sometimes, this barrier even blocks T cells and other therapies that could help kill brain tumours.

This immunosuppressive environment inside and around the glioblastoma is what makes common cancer therapies like pembrolizumab and chemotherapy significantly less effective in treating it. Tran theorised the best way to get around this issue was to start an immune reaction directly inside the tumour itself, an approach known as in situ immunisation, using TTFields.

This study demonstrates that combining TTFields with immunotherapy triggers a potent immune response within the tumour – one that ICIs can then amplify to bolster the body’s own defence against cancer.

“Think of it like a team sport – immunotherapy sends players in to attack the tumour (the offence), while TTFields weaken the tumour’s ability to fight back (the defence). And just like in team sports, the best defence is a good offence,” said Tran, who is also a member of the USC Norris Comprehensive Cancer Center.

Study methodology and results

The study analysed data from 2-THE-TOP, a Phase 2 clinical trial, which enrolled 31 newly diagnosed glioblastoma patients who had completed chemoradiation therapy. Of those, 26 received TTFields combined with both chemotherapy and immunotherapy. Seven of these 26 patients had inoperable tumours due to their locations – an especially high-risk subgroup with the worst prognosis and few treatment options.

Patients in the trial were given six to 12 monthly treatments of chemotherapy alongside TTFields for up to 24 months. The number and duration of treatments were determined by patients’ response to treatment. The immunotherapy was given every three weeks, starting with the second dose of chemotherapy, for up to 24 months.

Patients who used the device alongside chemotherapy and immunotherapy lived approximately 10 months longer than patients who had used the device with chemotherapy alone in the past. Moreover, those with large, inoperable tumours lived approximately 13 months longer and showed much stronger immune activation compared to patients who underwent surgical removal of their tumours.

“Further studies are needed to determine the optimal role of surgery in this setting, but these findings may offer hope, particularly for glioblastoma patients who do not have surgery as an option,” said Tran.

The researchers are now moving ahead to a Phase 3 trial.

Source: University of Southern California – Health Sciences

Categories : Cancer Obstetrics & GynaecologyTags :

Do Bevacizumab’s Ovarian Cancer Clinical Trial Results Hold up in the Real World?

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Photo by Tima Miroshnichenko on Pexels

A real-world study based on information from an electronic health records–derived database reveals limited benefits of adding bevacizumab to first-line chemotherapy for patients with ovarian cancer, consistent with previous clinical trials. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor A that acts to inhibit malignant cell growth and blood vessel formation. It’s approved as a treatment for various types of cancer. In clinical trials of patients with ovarian cancer, adding bevacizumab to first-line chemotherapy did not prolong overall survival compared with chemotherapy alone, but this treatment strategy did improve overall survival in analyses limited to patients with high-risk prognostic factors—such as those with advanced disease and those who had residual cancer present after surgery. A final long-term analysis did not find an overall survival benefit associated with bevacizumab in the full patient cohort.

To investigate whether these findings also hold true in real-world clinical practice, researchers examined the electronic health records of 1,752 patients with stage III or IV ovarian cancer who initiated chemotherapy with or without bevacizumab in 2017–2023 and were followed for a median time of 1.5 years.

Among patients with high-risk prognostic factors, the median time to next treatment was significantly longer for those receiving chemotherapy plus bevacizumab compared with those receiving chemotherapy alone: 13.6 versus 11.7 months. (Time to next treatment is used to assess the duration of clinical benefit by measuring the time between initiating a treatment and starting the next line of therapy). In these patients, there was also a trend towards longer median overall survival for the combination therapy: 31.1 versus 27.4 months. Among patients without high-risk prognostic factors, outcomes did not differ with the addition of bevacizumab. Benefits therefore seemed limited to special subpopulations, mirroring the findings from clinical trials.

“Our results were similar to results from clinical trials,” said lead author Linda R. Duska, MD, MPH, of the University of Virginia School of Medicine. “Our findings suggest that clinicians should consider a patient’s risk factors before using bevacizumab with first-line chemotherapy in the treatment of advanced ovarian cancer.”  

Source: Wiley

Categories : Cancer New Compounds and TreatmentsTags :

Scientific Breakthrough: Price of Costly Cancer Drug can be Halved

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Taxol is one of the most commonly prescribed chemotherapy drugs for breast, ovarian, cervical, and lung cancer. Yet producing the drug is complex, costly, and environmentally burdensome, as it currently relies on a complicated chemical semi-synthesis. For 30 years, scientists around the world have tried to understand how taxol, a natural compound derived from the Pacific yew tree, forms in nature. Decoding this process would allow for biotech-based production. But the final steps remained unknown – until now.

A research team from the University of Copenhagen has succeeded in finding the two missing pieces: They have identified the enzymes responsible for the two critical final steps in the biosynthetic pathway that makes Taxol active as a drug.

“Taxol has been the Holy Grail in this research field for decades because it’s an exceptionally complex molecule. But with the discovery of the final two enzymes, we now fully understand how it’s formed. This has allowed us to develop a biotechnological method to produce taxol in yeast cells,” says Sotirios Kampranis, Professor at the Department of Plant and Environmental Sciences and senior author of the study published in Nature Synthesis.

The method involves cloning the taxol-producing genes from the yew tree and inserting them into yeast cells. These engineered yeast cells then become host organisms or micro-factories with the full recipe to produce taxol.

Affecting women in developing countries

The research team from the University of Copenhagen has applied for patenting the method and is in the process of launching a spin-out company to manufacture biosynthetic Taxol. 

“Using this method, we can produce Taxol cheaper than current conventional methods. Looking ahead, once we refine the process further, we expect to be able to reduce the cost by half,” says Assistant Professor and first author Feiyan Liang.

Lower prices are especially crucial as ovarian cancer is on the rise globally. The prevalence of the disease is expected to increase by over 55% by 2050, with the vast majority of cases in low and middle-income countries. The number of women dying from ovarian cancer is projected to rise by nearly 70% in the same period.

Currently, taxol costs more than USD20 000 per kilogram, making it one of the most expensive active pharmaceutical ingredients in use.

“We see increasing demand for Taxol in many developing countries, where the high price is a major barrier. We hope our work will contribute to lower-priced drugs so that more people can have access to cancer treatment,” Feiyan Liang says.

Much more sustainable

The new method is not only more cost-effective but also more sustainable than chemical synthesis. One advantage is that the procedure does not involve harmful chemicals and solvents common in chemical production. Another advantage is that it allows the use of more crude, less purified extracts from yew needles as starting material – much cheaper than the ultra-pure inputs required in chemical semi-synthesis. On top of that, the materials can be recycled.

“We want to show that it’s possible to build a biotechnological drug production that is both sustainable and low-cost. There are very few examples of that today, but we now have the foundation to make it happen,” says Sotirios Kampranis. 

TWO TREES PER TREATMENT

  • Taxol was originally extracted from the inside bark of the Pacific yew tree (Taxus brevifolia), but as the taxol content in the bark is very low, harvesting it meant removing all the bark and as a result of this killing the tree.
  • Yew trees take 70 to 100 years to mature. Producing just one treatment required about two trees, making this method highly unsustainable. It was abandoned years ago, though wild yew trees are still under pressure in some regions.
  • Today’s most common method involves harvesting a similar compound from yew needles for chemical synthesis, but the cost of this process is still high, which is why the average price of taxol exceeds USD 20 000 per kilogram (source: pharmacompass.com).

Source: University of Copenhagen – Faculty of Science

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 : CancerTags :

An Inhalable Chemotherapy for Lung Cancer – Inspired by Mussels

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Researchers from POSTECH and Kyungpook National University have developed a novel inhalable therapeutic delivery system for lung cancer, making use of mucoadhesive protein nanoparticles inspired the adhesive properties of marine mussels.

Non-small cell lung cancer (NSCLC), which accounts for 85% of all lung cancer cases and treatment is particularly challenging due to difficulties in early detection. Current anticancer treatments are predominantly administered intravenously, impacting both malignant and healthy tissues, often leading to severe adverse effects. As a result, inhalable therapeutics have emerged as a promising alternative, enabling localised drug delivery directly to the lungs. A major obstacle to this approach is the lung’s mucosal barriers and immune cells. Building on this context, collaborative research has culminated in the development of a mucoadhesive protein nanoparticle designed for lung cancer treatment.

This approach leverages the remarkable adhesive properties of marine mussel proteins, renowned for their underwater adhesion. Drawing inspiration from the oxidation-reduction mechanisms of foot protein type 6 (fp-6), the researchers engineered foot protein type 1 (fp-1) by integrating cysteine, creating a biomaterial with enhanced adhesive strength and precise drug delivery capabilities within the lung cancer microenvironment. These nanoparticles exhibit exceptional therapeutic efficacy by enabling selective payload release while effectively inhibiting release in healthy tissues to minimise adverse effects. Moreover, the intrinsic biocompatibility, biodegradability, and immunocompatibility of marine mussel proteins ensure superior biological safety and substantially prolong the retention of anticancer drugs, thereby amplifying their therapeutic impact.

In animal models of lung cancer, the nanoparticles developed by the research team and their contained anti-cancer drugs showed effectiveness in inhibiting cancer cell metastasis and invasion after being delivered to the lungs through a nebuliser and adhering to the mucosa for extended periods. This advancement holds the potential to enhance patient access to lung cancer treatment, as the simplified inhalation-based drug administration could be self-managed at home. Furthermore, this approach may significantly improve patients’ quality of life by reducing the need for hospital visits.

Professor Hyung Joon Cha, who spearheaded the collaborative research at POSTECH, stated, “The findings from our study have the potential to substantially enhance both the precision and efficacy of lung cancer treatments, while significantly improving patients’ quality of life.”

Source: Pohang University of Science & Technology (POSTECH)

Categories : Cancer New Compounds and TreatmentsTags :

Magnetic Fields Boost Doxorubicin Uptake in Breast Cancer Treatment

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Colourised scanning electron micrograph of a breast cancer cell. Credit: NIH

Researchers at the National University of Singapore (NUS) have developed a non-invasive method to improve the effectiveness of chemotherapy while reducing its harmful side effects.

By applying brief, localised pulses of magnetic fields, the team demonstrated a significant increase in the uptake of doxorubicin (DOX), a widely used chemotherapy drug, into breast cancer cells, with minimal impact on healthy tissues. This selective uptake enables more precise targeting of cancer cells, potentially improving treatment outcomes and reducing the adverse effects often associated with chemotherapy.

The study, led by Associate Professor Alfredo Franco-Obregón at NUS, is the first to systematically show how pulsed magnetic fields enhance DOX uptake in cancer cells. The team also showed that this approach could suppress tumours at lower drug doses.

The team’s research was published in the journal Cancers. It builds on earlier work from 2022, which first revealed that certain cancer cells are more vulnerable to magnetic field therapy.

Better chemotherapy outcomes and fewer side effects

DOX is a commonly used chemotherapy drug for breast cancer. It works by binding to DNA components and disrupting cell replication and respiration, which then kills off cancer cells. Despite its efficacy, it is a non-selective drug, which means it can also damage healthy tissues, leading to side effects ranging from mild to severe, including cardiomyopathy and muscle atrophy.

To address these challenges, the NUS researchers developed a novel approach that uses brief pulses of magnetic fields to selectively increase DOX uptake into breast cancer cells. Their study revealed the role of a calcium ion channel known as TRPC1, which is often found in aggressive cancers, including breast cancer. Magnetic field exposure activates TRPC1, enhancing its ability to facilitate the entry of DOX into cancer cells.

The researchers conducted experiments comparing the effects of the magnetic field therapy on human breast cancer cells and healthy muscle cells. They found that breast cancer cells took in significantly more DOX when exposed to magnetic pulses, while normal tissues were not targeted as much. A 10-minute magnetic field exposure reduced the drug concentration needed for similar amount of cancer killing by half, particularly at low doses of the drug.

In contrast, healthy muscle cells did not show an increase in cell death in response to the combination of DOX and magnetic pulses indicating greater protection for non-cancerous tissues.

The team also demonstrated that reducing TRPC1 expression or blocking its activity eliminated this effect, which confirms the crucial role of TRPC1 channels in the process. “Importantly, when we increased the amount of TRPC1, we observed an increase in DOX uptake – this means that TRPC1 can be used as a viable therapeutic target for aggressive cancers,” said first author Mr Viresh Krishnan Sukumar, PhD candidate at NUS Centre for Cancer Research (N2CR).

“What’s promising is that this mechanism works strongest at low drug concentrations, enabling us to target cancer cells more effectively while reducing the burden of chemotherapy on healthy tissues,” Assoc Prof Franco-Obregón added.

With breast cancer remaining the leading cause of cancer-related deaths among women worldwide, the need for novel treatment strategies is urgent. “The majority of women who undergo chemotherapy experience side effects from treatment, and in some cases, doses of chemotherapy need to be reduced, or in severe cases, stopped prematurely,” said Assistant Professor Joline Lim, Principal Investigator at N2CR and Senior Consultant, Department of Haematology-Oncology, National University Cancer Institute, Singapore. “Moreover, prolonged exposure to high-dose chemotherapy can also lead to drug resistance. This targeted approach represents an excellent opportunity to potentially improve treatment outcomes while preserving patients’ quality of life.”

Advancing the frontier of precision oncology

The team’s magnetic-assisted approach addresses one of the biggest challenges of chemotherapy, namely its toxic effects on healthy tissues. By selectively enhancing drug uptake into cancer cells, this method has the potential to drastically reduce the systemic side effects often experienced by breast cancer patients. This not only improves treatment outcomes and quality of life, but also encourages earlier treatment for those hesitant about treatment side effects. The study also underscores the role of biomarkers, such as elevated TRPC1 expression, in transforming cancer care by enabling precision-driven treatment options.

Future work will focus on translating these findings into clinical practice by localising magnetic field exposure specifically to tumours in patients. This would further validate the potential to reduce systemic DOX doses while maximising localised drug delivery in cancer cells.

“Our approach will be patented and form the foundation for a startup specialising in breast cancer treatment. We are currently in discussions with potential investors in Southeast Asia and the United States to translate this technology from bench to bedside,” shared Assoc Prof Franco-Obregón. National University Cancer Institute, Singapore. “Moreover, prolonged exposure to high-dose chemotherapy can also lead to drug resistance. This targeted approach represents an excellent opportunity to potentially improve treatment outcomes while preserving patients’ quality of life.”

Source: National University of Singapore

Categories : Cancer New Compounds and TreatmentsTags :

Gold Trumps Platinum for Chemotherapy Compounds

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Left: Normal cervical cancer cells with well-formed nuclei in blue and elongated actin filaments – which play an essential role in cell survival and division – in green. Right: Destabilised cervical cancer cells after gold compound treatment show structural integrity compromised while the nuclei in blue are breaking apart, indicating cell death. Credit: RMIT University

Gold-based drugs can slow tumour growth in animals by 82% and target cancers more selectively than standard chemotherapy drugs, according to new research out of RMIT University. The study published in the European Journal of Medicinal Chemistry reveals a new gold-based compound that’s 27 times more potent against cervical cancer cells in the lab than standard chemotherapy drug cisplatin. 

It was also 3.5 times more effective against prostate cancer and 7.5 times more effective against fibrosarcoma cells in the lab. In mice studies, the gold compound reduced cervical cancer tumour growth by 82%, compared to cisplatin’s 29%. 

Project lead at RMIT, Distinguished Professor Suresh Bhargava AM, said it marked a promising step towards alternatives to platinum-based cancer drugs.  

“These newly synthesised compounds demonstrate remarkable anticancer potential, outperforming current treatments in a number of significant aspects including their selectivity in targeting cancer cells,” said Bhargava, Director of RMIT’s Centre for Advanced Materials and Industrial Chemistry. “While human trials are still a way off, we are really encouraged by these results.” 

The gold-based compound is patented and ready for further development towards potential clinical application.

Gold: the noblest element

Photo by Jingming Pan on Unsplash

Gold is famously known as the noblest of all metals because it has little or no reaction when encountering other substances. However, the gold compound used in this study is a chemically tailored form known as Gold(I), designed to be highly reactive and biologically active.  

This chemically reactive form was then tailored to interact with an enzyme abundant in cancer cells, known as thioredoxin reductase.

By blocking this protein’s activity, the gold compound effectively shuts down cancer cells before they can multiply or develop drug resistance. 

Project co-lead at RMIT, Distinguished Professor Magdalena Plebanski, said along with this ability to block protein activity, the compound also had another weapon in its anti-cancer arsenal. 

In zebrafish studies, it was shown to stop the formation of new blood vessels that tumours need in order to grow. 

This was the first time one of the team’s various gold compounds had shown this effect, known as anti-angiogenesis.  

The drug’s effectiveness at using these two attacks simultaneously was demonstrated against a range of cancer cells. 

This included ovarian cancer cells, which are known to develop resistance to cisplatin treatment in many cases. 

“Drug resistance is a significant challenge in cancer therapy,” said Plebanski, who heads RMIT’s Cancer, Ageing, and Vaccines Laboratory.

“Seeing our gold compound have such strong efficacy against tough-to-treat ovarian cancer cells is an important step toward addressing recurrent cancers and metastases.” 

Gold has been a cornerstone of Indian Ayurvedic treatments for centuries, celebrated for its healing properties. Today, gold-based cancer treatments are gaining global traction, with advancements such as the repurposing of the anti-arthritic drug auranofin, now showing promise in clinical trials for oncology. 

“We know that gold is readily accepted by the human body, and we know it has been used for thousands of years in treating various conditions,” Bhargava said.

“Essentially, gold has been market tested, but not scientifically validated. 

“Our work is helping both provide the evidence base that’s missing, as well as delivering new families of molecules that are tailor-made to amplify the natural healing properties of gold,” he said.

Bhargava said this highly targeted approach minimises the toxic side effects seen with the platinum-based cisplatin, which targets DNA and damages both healthy and cancerous cells.

“Their selectivity in targeting cancer cells, combined with reduced systemic toxicity, points to a future where treatments are more effective and far less harmful,” Bhargava said. 

This specific form of gold was also shown to be more stable than those used in earlier studies, allowing the compound to remain intact while reaching the tumour site. 

Categories : Cancer ExerciseTags :

Aerobic Exercise may Help Prevent the Brain Fog from Chemotherapy

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Clinical trial reveals improved self-reported cognitive function in women with breast cancer who started an exercise program when initiating chemotherapy.

Photo by Ketut Subiyanto on Pexels

Many women who receive chemotherapy experience a decreased ability to remember, concentrate, and/or think – commonly referred to as “chemo-brain” or “brain fog” – both short- and long-term. In a recent clinical trial of women initiating chemotherapy for breast cancer, those who simultaneously started an aerobic exercise program self-reported greater improvements in cognitive function and quality of life compared with those receiving standard care. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

The study, called the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial, included 57 Canadian women in Ottawa and Vancouver who were diagnosed with stage I–III breast cancer and beginning chemotherapy. All women participated in 12–24 weeks of aerobic exercise: 28 started this exercise when initiating chemotherapy and 29 started after chemotherapy completion. Cognitive function assessments were conducted before chemotherapy initiation and after chemotherapy completion (therefore, before the latter group started the exercise program).

Women who participated in the aerobic exercise program during chemotherapy self-reported better cognitive functioning and felt their mental abilities improved compared with those who received standard care without exercise. Neuropsychological testing – a performance-based method used to measure a range of mental functions – revealed similar cognitive performance in the two groups after chemotherapy completion, however.

“Our findings strengthen the case for making exercise assessment, recommendation, and referral a routine part of cancer care; this may help empower women living with and beyond cancer to actively manage both their physical and mental health during and after treatment,” said lead author Jennifer Brunet, PhD, of the University of Ottawa.

Dr Brunet noted that many women undergoing chemotherapy for breast cancer remain insufficiently active, and there are limited exercise programs tailored to their needs. “To address this, we advocate for collaboration across various sectors – academic, healthcare, fitness, and community – to develop exercise programs specifically designed for women with breast cancer,” she said. “These programs should be easy to adopt and implement widely, helping to make the benefits of exercise more accessible to all women facing the challenges of cancer treatment and recovery.”

Source: Wiley

Categories : Cancer Metabolic DisordersTags :

The Outcomes of Cancer Therapies and BMI Have a Complex Relationship

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Risk of mortality during cancer treatment in relation to BMI. For non-small cell lung cancer treatment, immunotherapy seems to pose less risk for persons under a certain BMI, while conventional chemotherapy appears optimal for persons who might be overweight or obese. Credit: Osaka Metropolitan University

While being overweight increases the risk of developing lifestyle-related diseases, there is a phenomenon known as the obesity paradox where a decreased risk of death has been seen during cancer therapy. However, that paradox might not hold true for all cancer therapies, an Osaka Metropolitan University team reports in JAMA Network Open, a publication of the American Medical Association.

Led by graduate student Mr Yasutaka Ihara and Professor Ayumi Shintani of the Graduate School of Medicine’s Department of Medical Statistics, the team used a Japanese administrative claims database of more than 500 000 lung cancer patients and examined the relation between body mass index (BMI) and the risk of mortality during immunotherapy and conventional chemotherapy.

Focusing only on patients with advanced non-small cell lung cancer, the team found that the higher the BMI, the lower the risk of mortality when undergoing both immunotherapy and chemotherapy, though it does a U-turn around a BMI of 24. Patients with a BMI under 28 showed lower risk of mortality when undergoing immunotherapy compared to conventional chemotherapy, but for those at or over that figure, the risk increases with immunotherapy while it continues to get lower with chemotherapy.

“Immunotherapy might not always be the optimal treatment method for obese patients with advanced non-small cell lung cancer, so the use of conventional chemotherapy should also be considered,” Mr. Ihara stated. “In addition to BMI, age, hormones, and gut microbiota have been reported as factors that influence the effectiveness of immunotherapy. Evaluation of whether immunotherapy or conventional chemotherapy improves survival in the presence of these factors is expected to contribute to the development of precision medicine.”

Source: Osaka Metropolitan University

Categories : CancerTags :

When is the Best time of Day for Chemotherapy?

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Researchers from Charité are developing new methods to use the internal clock inside tumour cells to optimise cancer therapies

One of the factors determining the effectiveness of certain medications depends on various factors, including the time of day when they are administered. This is due to circadian rhythms, which vary across individuals and makes it difficult to tailor medication schedules. Researchers at Charité – Universitätsmedizin Berlin have now developed a method for determining the optimum time of cancer treatment based on certain breast cancer cell lines. They describe their approach in the journal Nature Communications.

As well as bodily functions and metabolic processes, such as sleep and digestion, individual cells also follow a circadian rhythm. This is hugely important to chemotherapy. Previous studies have shown that chemotherapy is most effective when the tumour cells are dividing. But this finding has been hardly used at all in clinical treatment to date.

An interdisciplinary team at Charité headed by Dr. Adrián Enrique Granada from the Charité Comprehensive Cancer Center (CCCC) set out to close this gap. The team began looking for the optimum time to administer medication, based on the individual circadian rhythms of the tumors.

Triple-negative breast cancer as an example

“We cultured cells from patients with triple-negative breast cancer to observe how they respond at different times of day to the medications administered,” explains Carolin Ector, a research associate in Granada’s working group. Triple-negative breast cancer is a highly aggressive form of breast cancer, with few effective treatments available. “We used live imaging, a method of continuously monitoring living cells, and complex data analysis techniques to monitor and evaluate the circadian rhythms, growth cycles, and medication responses of these cancer cells in detail.”

In this way, the researchers identified certain times of the day at which cancer cells are most responsive to medication-based treatments. For example, the chemotherapeutic drug 5-fluorouracil (5-FU) turned out to have peak efficacy against a certain cancer cell line between eight and ten a.m. As the study also shows, the crucial aspects here are certain cellular and genetic factors. The scientists were even able to identify which genes are key to the circadian effects of certain medications. “We call them ‘core clock genes’. They have a significant impact on how responsive cancer cells are to treatments administered at different times of day,” Granada explains.

Profiles show how cancer cell types respond to medications

This approach can be used to create detailed profiles showing how different types of cancer cells respond to different medications at various times. “This can help to identify the most effective combinations of drugs,” Granada says. “Overall, our findings indicate that personalized treatment plans based on individual circadian rhythms could substantially improve the efficacy of cancer treatment”, he concludes. Moreover, undesirable side effects could also be reduced.

For these findings to contribute to clinical practice soon, the results should be validated in studies involving larger groups of patients. “We’re also planning to study the molecular mechanisms behind the circadian influences on medication sensitivity to further optimize treatment times and identify new therapeutic targets,” Granada says.

Source: Charité – Universitätsmedizin Berlin