Tag: chemotherapy

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

Categories : Cancer ExerciseTags :

Physical Exercise Concomitant with Chemotherapy Reduces Nerve Damage

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Photo by Mikhail Nilov

Many cancer medications, from chemotherapy to modern immunotherapies, attack the nerves as well as the tumour cells. Some therapies, such as oxaliplatin or vinca alkaloids, leave 70 to 90% of patients complaining of pain, balance issues, or feelings of numbness, burning or tingling. These symptoms can be very debilitating. They can disappear following cancer treatment, but in around 50% they become chronic. Specialists call it chemotherapy-induced peripheral neuropathy, or CIPN for short.

A research team led by sports scientist Dr Fiona Streckmann from the University of Basel and the German Sport University Cologne has now shown that specific exercise, concomitant to cancer therapy, can prevent nerve damage in many cases. The researchers have reported their findings in JAMA Internal Medicine.

Exercise alongside chemo

The study involved 158 cancer patients, both male and female, who were receiving treatment either with oxaliplatin or vinca-alkaloids. The researchers divided the patients at random into three groups. The first was a control group, whose members received standard care. The other two groups completed exercise sessions twice a week for the duration of their chemotherapy, with each session lasting between 15 and 30 minutes. One of these groups carried out exercises that focused primarily on balancing on an increasingly unstable surface. The other group trained on a vibration plate.

Regular examinations over the next five years showed that in the control group around twice as many participants developed CIPN as in either of the exercise groups. In other words, the exercises undertaken alongside chemotherapy were able to reduce the incidence of nerve damage by 50 to 70%. In addition, they increased the patients’ subjectively perceived quality of life, made it less necessary to reduce their dose of cancer medications, and reduced mortality in the five years following chemotherapy.

The participants receiving vinca-alkaloids and performing sensorimotor training, had the largest benefit. 

Ineffective medications

A lot of money has been invested over the years in reducing the incidence of CIPN, explains Streckmann. “This side effect has a direct influence on clinical treatment: for example, patients may not be able to receive the planned number of chemotherapy cycles that they actually need, the dosage of neurotoxic agents in the chemotherapy may have to be reduced, or their treatment may have to be terminated.”

Despite the investments made, there is no effective pharmacological treatment to date: various studies have shown that medications can neither prevent nor reverse this nerve damage. However, according to the latest estimates, USD 17 000 are spent per patient every year in the USA on treating nerve damage associated with chemotherapy. Streckmann’s assumption is that “doctors prescribe medications despite everything, because patients’ level of suffering is so high.”

Study ongoing in children’s hospitals

In contrast, the sports scientist emphasises, the positive effect of exercise has been substantiated, and this treatment is very cheap in comparison. At the moment she and her team are working on guidelines for hospitals, so that they can integrate the exercises into clinical practice as supportive therapy. In addition, since 2023 a study has been ongoing in six children’s hospitals in Germany and Switzerland (Project PrepAIR), which is intended prevent sensory and motor dysfunctions in children receiving neurotoxic chemotherapy.

“The potential of physical activity is hugely underestimated,” says Fiona Streckmann. She very much hopes that the results of the newly published study will lead to more sports therapists being employed in hospitals, in order to better exploit this potential.

Source: University of Basel

Categories : CancerTags :

Chemo Drug may Cause Significant Hearing Loss in Longtime Cancer Survivors   

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Photo by Brett Sayles

An interdisciplinary study led by researchers at the University of South Florida and Indiana University has uncovered significant findings on the long-term effects of one of the most common forms of chemotherapy on cancer survivors.

Published in JAMA Oncology, the study tracked a cohort of testicular cancer survivors who received cisplatin-based chemotherapy. The team followed the patients for an average of 14 years, revealing that 78% experience significant difficulties in everyday listening situations, negatively impacting their quality of life. This collaborative research is the first to measure real-world listening challenges and hearing loss progression in cancer survivors over a long period of time.

“It’s important that we understand the real-world effects of patients’ sensory problems and if we can understand that, then we can develop better therapeutic strategies and preventive measures to improve the long-term quality of life for cancer survivors,” said Robert Frisina, distinguished university professor and chair of the USF Department of Medical Engineering.

Cisplatin is commonly used in chemotherapy treatments for a variety of cancers, including bladder, lung, neck and testicular. It is administered intravenously and affects various parts of the body. However, the ears are particularly vulnerable as they have little ability to filter out the drug, causing it to become trapped. This leads to inflammation and the destruction of sensory cells that are critical for coding sound, causing permanent hearing loss that can progressively get worse well after cisplatin treatments are completed.

Lead author Victoria Sanchez, associate professor in the USF Health Department of Otolaryngology Head & Neck Surgery, said that despite the known risks, there’s a nationwide lack of routine hearing assessments for patients undergoing chemotherapy. “Most patients still do not get their hearing tested prior to, during or after chemotherapy. Our study highlights the need for regular auditory evaluations to manage and mitigate long-term hearing damage.”

The research team found higher doses of cisplatin led to more severe and progressing hearing loss, especially in patients with risk factors, such as high blood pressure and poor cardiovascular health. They also experienced increased difficulty hearing in common environments, such as a loud restaurant.

“It will be critically important to follow these patients for life. Their current median age is only 48 years, and eventually they will enter the years at which age-related hearing loss also begins to develop,” said Dr. Lois B. Travis, Lawrence H. Einhorn Professor of Cancer Research at Indiana University School of Medicine and a researcher at the IU Melvin and Bren Simon Comprehensive Cancer Center. This research is part of The Platinum Study, an ongoing research effort led by Dr. Travis and funded by the National Cancer Institute to study cisplatin-treated testicular cancer survivors.

The hope is that this study will inspire further investigation into alternative chemotherapeutic protocols and preventive measures, such as FDA-approved drugs to prevent or reduce hearing loss.

“This research gives oncologists the information they need to explore alternative treatment plans that could reduce the long-term side effects, such as altering the dosages and timing of the cisplatin in the treatment, when that could be an appropriate option,” Frisina said.

Innovative solutions, such as Pedmark, a new FDA-approved injection that mitigates cisplatin-induced hearing loss in children, represent promising steps forward, according to Frisina.

“We want to protect our hearing or treat a hearing loss if hearing damage occurs,” Sanchez said. “Hearing allows us to connect to the world we love. Staying connected through conversations with family and friends, enjoyment of music and entertainment, staying safe and finding pleasure in our vibrant surroundings. Promoting optimal hearing for overall wellness is essential for healthy living.”

According to the American Cancer Society, in addition to cisplatin, other platinum chemotherapy drugs, such as carboplatin, cause damage to the cochlea in the inner ear and lead to hearing loss. The risk of damage is greater with higher doses of chemotherapy.

Source: University of San Francisco

Categories : CancerTags :

Chemotherapy Before Surgery Extends Survival in Pancreatic Cancer

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

Patients with pancreatic cancer who received chemotherapy both before and after surgery experienced longer survival rates than would be expected from surgery followed by chemotherapy, according to a new study from researchers at Yale School of Medicine.

The study, published June 20 in JAMA Oncology, included patients with pancreatic ductal adenocarcinoma (PDAC), an aggressive cancer with a high mortality rate which accounts for 90% of pancreatic cancers. The researchers say these findings are encouraging for the 15 to 20% of patients with operable pancreatic cancer.

The single-arm Phase II trial evaluated a modified form of the chemotherapy treatment FOLFIRINOX. This combination treatment consisting of leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin received US Food and Drug Administration approval in 2011 as a first-line treatment for patients with metastatic pancreatic cancer. Patients in the trial received six cycles of the modified FOLFIRINOX before surgery, followed by an additional six cycles of the chemotherapy treatment after surgery. The modified regimen consisted of slightly lower doses of FOLFIRINOX to improve tolerability, which was previously shown in a 2016 publication not to impact outcomes negatively.

Of the 46 patients who started the modified treatment, 37 completed all six cycles of chemotherapy before surgery and 27 had successful tumour removal operations. For all enrolled patients, the 12-month progression-free survival rate was 67%, indicating significant progress in controlling the disease. Furthermore, 59% of all patients lived at least two years after completing the full chemotherapy treatment plan and surgery.

The study was the first of its kind for patients with PDAC when senior author and Yale Cancer Center member Jill Lacy, MD, started it in 2014. The study goal had been a 12-month progression-free survival rate of at least 50% of patients.

“When the study launched, even with operable pancreatic cancers, 90% of patients were still relapsing and dying from their cancer eventually,” said Michael Cecchini, MD, the first author of the study. “We sought to move chemotherapy up in their treatment regimen and give it before surgery to see if we could improve the outcome for our patients.”

The study used advanced techniques to monitor the progress of treatment, including analysing circulating tumour DNA (ctDNA) and using the cancer biomarker keratin 17 to help predict outcomes. For example, patients with detectable ctDNA four weeks post-surgery had significantly worse progression-free survival than those who had no detectable ctDNA.

Cecchini said larger randomised clinical trials are needed to continue to investigate the role of FOLFIRINOX before surgery for patients with operable PDAC.

“I think even though there have been changes in standard of care for patients with this aggressive pancreatic cancer type, we have here very promising data to justify a larger study,” said Cecchini.

Source: Yale School of Medicine

Categories : Cancer Cardiovascular DiseaseTags :

New Discovery in Preventing Heart Damage from Chemotherapy

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Human heart. Credit: Scientific Animations CC4.0

Blocking a protein known as CDK7 could prevent heart damage associated with the commonly used cancer chemo drug doxorubicin, according to a study led by scientists at Washington State University. Importantly, the researchers also found that inhibiting CDK7 could help enhance the drug’s cancer-killing capability.

Based on an animal model, the study findings could provide a foundation for future treatment strategies to reduce chemotherapy-related heart toxicity and increase treatment effectiveness. This could ultimately help increase the lifespan of people with cancer. Heart damage related to chemotherapy treatment can surface decades after treatment and can result in heart attacks, heart failure, cardiomyopathy and other types of heart disease.

Published in the journal Cardiovascular Research, the WSU study focused on doxorubicin, a chemotherapy drug used to treat breast cancer, lymphoma, leukaemia and other cancers. Capable of killing a wide range of cancer cells, doxorubicin and other similar chemotherapy medications are known to be toxic to the heart. Despite this toxicity, the drug still sees a lot of use.

“Doxorubicin remains the mainstay treatment for certain cancer types for which targeted therapies or other better treatments are not available,” said senior study author Zhaokang Cheng, an associate professor in the WSU College of Pharmacy and Pharmaceutical Sciences.

Cheng has been working to unravel the underlying mechanisms of doxorubicin-induced heart toxicity to make the use of doxorubicin safer for patients who rely on the drug. This new study builds on findings from earlier research that showed that doxorubicin activates a protein known as CDK2. That protein then activates another known as FOXO1, which causes heart cells to die. Cheng’s team collaborated with WSU cancer biology researcher Boyang (Jason) Wu to take a closer look at CDK7, a protein that helps fuel cell growth and has been shown to play a role in the development of cancer.

The researchers found that CDK7 activated CDK2, which set off the chain of molecular signals that eventually led to heart cell death. They also showed that mice that lacked the CDK7 gene were protected from doxorubicin-induced heart toxicity. Next, they used a CDK7 inhibitor drug known as THZ1 to block the protein’s activity and examine the impact on heart health and cancer growth. A similar inhibitor is currently being tested as an anticancer drug in clinical trials, but its effect on the heart is still not clear.

“We are the first to study the effect of THZ1 on the heart and on tumor growth in the same model,” said study first author Jingrui Chen, a WSU research associate. “And what we found is that this CDK7 inhibitor drug can increase heart function and at the same time inhibit tumour growth.”

Though more research is needed, the researchers said their findings suggest that combining doxorubicin and THZ1 could help prevent heart damage and increase the effectiveness of chemotherapy treatment.

The researchers’ next step is to test the effect of THZ1 on heart damage and cancer growth in younger mice and follow them longer. This would more closely mimic long-term doxorubicin-induced heart toxicity seen in childhood cancer survivors. They also plan to look at other proteins that may somehow be involved in the signaling pathway that underlies doxorubicin-related heart damage.

Source: Washington State University

Categories : Cancer New Compounds and TreatmentsTags :

New Treatment Quadruples 3-year Survival for Rare and Aggressive Cancer

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Photo by National Cancer Institute on Unsplash

An innovative treatment significantly increases the survival of people with malignant mesothelioma, a rare but rapidly fatal type of cancer with few effective treatment options, according to results from a clinical trial led by Queen Mary University of London and published in JAMA Oncology.

The phase 3 clinical trial, led by Professor Peter Szlosarek at Queen Mary and sponsored by Polaris Pharmaceuticals, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), a rare and often rapidly fatal form of cancer with limited therapeutic options.

The ATOMIC-meso trial, a randomised placebo-controlled study of 249 patients with MPM, found that a treatment – which combines a new drug, ADI-PEG20, with traditional chemotherapy – increased the median survival of participants by 1.6 months, and quadrupled the survival at 36 months, compared to placebo-chemotherapy.

The findings are significant, as MPM has one of the lowest 5-year survival rates of any solid cancer of around 5-10%. This innovative approach marks the first successful combination of chemotherapy with a drug that targets cancer’s metabolism developed for this disease in 20 years.

MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with exposure to asbestos. It’s usually treated with potent chemotherapy drugs, but these are seldom able to halt the progression of the disease.

The premise behind this new drug treatment is elegant in its simplicity – starving the tumour by cutting off its food supply. All cells need nutrients to grow and multiply, including amino acids like arginine. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumour cells that can’t manufacture their arginine due to a missing enzyme, this means their growth is thwarted.

The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary’s Barts Cancer Institute that began with Professor Szlosarek’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. He and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM.

Professor Szlosarek said: “It’s truly wonderful to see the research into the arginine starvation of cancer cells come to fruition. This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma. I thank all the patients and families, investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy.”

There are ongoing studies assessing ADI-PEG20 in patients who have sarcoma or glioblastoma multiforme and other cancers dependent on arginine. The success of this novel chemotherapy in MPM also suggests that the drug may be of benefit in the treatment of multiple other types of cancer. 

Source: Queen Mary University London

Categories : Cancer Cardiovascular DiseaseTags :

Clues to Ponatinib’s Deadly Side Effects could Make it a Safer Cancer Drug

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For some leukaemia patients, the only potential chemotherapy option is ponatinib, a drug that also carries a high risk of heart failure. This means that some patients who recover from their cancer will end up dying of heart disease brought on by the cure.

In a new study, researchers from the University of Illinois Chicago and other universities have identified mechanisms that cause ponatinib to harm the heart. They also identified a promising treatment that could reverse this process.

The paper, with senior author Sang Ging Ong, assistant professor of pharmacology and medicine at UIC, is published in Circulation Research. The study is part of a growing field called cardio-oncology that investigates drugs that shrink tumours but can also cause heart problems.

While there are three options of drugs for treating chronic myeloid leukaemia, many patients are resistant to the other two, leaving ponatinib as their only choice.

“These patients have no other options for treatment,” Ong said, despite the concerns about the drug’s side effects.

In fact, ponatinib was pulled from the market for a few months after its introduction in 2012 because of concerns about heart problems.

The researchers were interested in understanding the interaction between ponatinib and the heart cells responsible for contraction.

They discovered that ponatinib damages these cells by activating a process known as the integrated stress response.

The mechanism for this is related to the functioning of a kinase (an enzyme involved in energy transfer) called GCN2.

The researchers found that ponatinib, despite being a kinase inhibitor, actually activates GCN2, which in turn switches on the integrated stress response.

While this response isn’t always a bad thing, normally protecting cells, it can also lead to their death under prolonged stress.

To see if this response was harming the cells, the researchers studied what would happen if they used a small molecule to block the integrated stress response in both cells and in mice during ponatinib treatment.

They found that the treatment helped protect heart cells from the damaging side effects of the drug yet did not diminish ponatinib’s tumour-fighting efficacy.

“It protects the heart but at the same time, it still allows us to kill cancer cells,” Ong said.

More research is needed to know if this protective measure would work well in humans, Ong said.

The mechanisms they identified are important in other cardiac diseases, as well, which could lead to future research on how to protect cells against different conditions.

Source: University of Illinois Chicago