Category: Cancer

Categories : CancerTags :

Endometrial Cancer on the Rise among Women of African Descent

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Compared with white women, Black women have elevated risks of being diagnosed with advanced uterine cancer – also known as endometrial cancer – and of developing aggressive tumours. Researchers recently compared the incidence and trends for endometrial cancer, both overall and by subtype, between African descent women in Florida and women in the French Caribbean, specifically, the islands of Martinique and Guadeloupe. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Endometrial cancer is classified as endometrioid or non-endometrioid (a more aggressive form) based on tumour cells’ appearance and genetic alterations. When Heidy N. Medina, PhD, MPH, of the University of Miami School of Medicine, and her colleagues analysed data on 34 789 endometrial cancer cases from Florida (US) and the French Caribbean from 2005–2018, they observed the following: 

  • Caribbean Black women had the lowest rates for both endometrioid and non-endometrioid subtypes.  
  • Non-endometrioid types were most common among US Black women (9.2 per 100 000), 2.6-times greater than the rate for US white women.  
  • For endometrioid cancer, rates increased 1.8% yearly from 2005–2018 for US Black women and 1.2% for US white women, while no change was observed for Caribbean Black women.  
  • For the more aggressive non-endometrioid cancers, rates increased among all women: 5.6% yearly among US Black women, 4.4% among Caribbean Black women, and 3.9% among US white women. 

“This study informs the current scientific evidence about endometrial cancer risk among a diverse sample of African descent women, highlighting that within group differences matter among Black women,” said Dr Medina. “Our study suggests that these differences among Black women in different regions of the world are partly due to social factors associated with assigned race rather than purely African ancestry – related factors based on genetic origin.”

Dr Medina added that the study emphasises the need to not generalise results from Black women in the US to other African descent populations worldwide where limited data exist. “This signals the need for coordinated efforts around the world in identifying disparities, emphasising the importance of strong cancer surveillance systems and registries throughout different regions, and the necessity for there to be a greater priority among the global health community in allocating resources to improve data collection for cancer registries worldwide,” she said.

Dr Medina also stressed the importance of tracking the increasing rates of the deadlier non-endometrioid types of endometrial cancer and identifying risk factors associated with these malignancies. 

Source: Wiley

Categories : CancerTags :

New Radiotherapy Technique Hits The Bullseye on Tumours

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Researchers in Japan have developed a new radiotherapy technique that has the potential to treat several kinds of cancer, with fewer negative side effects than currently available methods. Published in Chemical Science, the proof-of-concept study showed that tumours in mice grew almost three times less and survival was 100% after just one injection of an alpha-particle emitting radioisotope inside of cancer cells, killing them but sparing healthy tissue.

The side effects of standard chemotherapy and radiation treatment can be devastating, and the eradication of all cancer cells is not guaranteed, especially when the cancer has already metastasised and spread throughout the body. Therefore, the goal of most research these days is to find a way to specifically target cancer cells so that treatments only affect tumours. Some targeted treatments do exist, but they cannot be applied to all cancers. Researchers led by Katsunori Tanaka at the RIKEN Cluster for Pioneering Research (CPR) in Japan and Hiromitsu Haba at the RIKEN Nishina Center for Accelerator-Based Science (RNC) developed this new approach.

“One of the greatest advantages of our new method,” says Tanaka, “is that it can be used to treat many kinds of cancer without any targeting vectors, such as antibodies or peptides.”

The new technique relies on basic chemistry and the fact that a compound called acrolein accumulates in cancer cells. A few years ago, Tanaka’s team used a similar technique to detect individual breast cancer cells. They attached a fluorescent compound to a specific type of azide – an organic molecule with a group of three nitrogen atoms (N3) at the end. When the azide and acrolein meet inside a cancer cell, they react, and the fluorescent compound becomes anchored to structures inside the cancer cell. Because acrolein is almost absent from healthy cells, this technique acted like a probe to light up cancer cells in the body.

In the new study, rather than simply detecting cancer cells, the team targeted those cells for destruction. The logic was fairly simple. Instead of attaching the azide to a fluorescent compound, they attached it to something that can kill a cell without harming surrounding cells. The chose to work with astatine-211, a radionuclide that emits a small amount of radiation in the form of an alpha particle as it decays. Compared to other forms of radiation therapy, alpha particles are a little more deadly, but they can only travel about one twentieth of a millimetre and can be stopped by a piece of paper. In theory, when astatine-211 is anchored to the inside a cancer cell, the emitted alpha particles should damage the cancer cell, but not much beyond.

Once the team figured out the best way to attach astatine-211 to the azide probe, they were able to perform a proof-of-concept experiment to test their theory. They implanted human lung-tumour cells into mice and tested the treatment under three conditions: simply injecting astatine-211 into the tumour, injecting the astatine-211-azide probe into the tumour, and injecting the astatine-211-azide probe into the bloodstream. The found that without targeting, tumours continued to grow, and mice did not survive. As expected, when the azide probe was used, tumours grew almost three times less and many more mice survived – 100% when it was injected into the tumour and 80% when injected into the blood.

“We found that just one tumour injection with only 70kBq of radioactivity was extremely effective at targeting and eliminating tumour cells,” says Tanaka. “Even when injecting the treatment compound into the bloodstream, we were able to achieve similar results. This means we can use this method to treat very early-stage cancer even if we don’t know where the tumour is.” The fluorescent probe version of this technique is already being tested in clinical trials as a way of visualising and diagnosing cancer at the cellular level. The next step is to find a partner and begin clinical trials using this new method to treat cancer in humans.

Source: RIKEN

Categories : Cancer ImmunologyTags :

Researchers Discover an Anti-tumour Regulator on B Cells

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Melanoma Cells. Credit: National Cancer Institute

B cells are thought to play a critical role in innate and adaptive immunity, but their exact role in anti-tumour immunity remains unknown. Looking at B cells with a technique called single-cell profiling, which looks at all the genes in the cell, researchers found a protein that – when deleted – reduced tumour growth. The researchers write in Nature that this regulator could be a target for new cancer treatments.

The team, consisting of immunologists at Brigham and Women’s Hospital and dermatologists from Massachusetts General Hospital, identified a subset of B cells that expands specifically in the draining lymph node over time in mice with melanoma tumours.

They found a cell surface receptor called TIM-1 expressed on these B cells during melanoma growth. They also characterised multiple accompanying cell surface proteins that were involved in the B cell’s immune function. Interestingly, they found that deleting a molecule TIM-1, but not any of the other accompanying proteins, dramatically decreased tumour growth. The researchers concluded that TIM-1 controls B cell activation and immune response that combats cancer, including activating another type of the killer tumour-specific T cells for inhibiting tumour growth.

“The collaboration across institutions was extremely fruitful as we combined our immunology expertise at the Brigham with work at David Fisher’s MGH laboratory where seminal discoveries in skin malignancies have been made,” said lead author Lloyd Bod, PhD, of the Department of Neurology at the Brigham, who conducted this work while completing his postdoctoral fellowship at the Brigham. “The collaboration allowed us to test and demonstrate the therapeutic potential of targeting TIM-1 in melanoma models.”

Source: Mass General Brigham

Categories : CancerTags :

Five-year Survival Rates for Women with Early Stage Invasive Breast Cancer Have Tripled

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Significant advances in breast cancer treatment have improved care to the point where most women with an early invasive breast cancer diagnosis can expect to be survivors. A new study involved half a million women in England has found that in England, the cumulative mortality within five years of an early invasive breast cancer diagnosis has fallen from roughly 14% in the 1990s to just under 5% for women diagnosed in 2010–2015. The findings, published in The BMJ, also serve to identify the cases with the greatest risks, and point to the need for progressively larger study sizes for new treatments.

Annually, more than 2 million patients receive a diagnosis of invasive breast cancer around the world. For most, it is their first cancer. Most have early stage disease and receive surgery as their first treatment. Post-treatment outcomes vary widely across patient characteristics and countries. In order to inform treatment, follow-up and likely outcomes, more detailed mortality estimates were needed.

To address this, the researchers conducted a retrospective population based cohort study of 512 447 women, looking at diagnoses made within four time periods: 1993–99, 2000–04, 2005–09, and 2010–15. They examined annual breast cancer mortality rates and cumulative risks by time since diagnosis, calendar period of diagnosis, and nine characteristics of patients and tumours.

Across all time periods, the crude annual breast cancer mortality rate was highest during the five years after diagnosis and then declined. For any given time since diagnosis, crude annual breast cancer mortality rates and risks decreased with increasing calendar period. Crude five year breast cancer mortality risk was 14.4% for women with a diagnosis made during 1993-99 and 4.9% for women with a diagnosis made during 2010-15.

Adjusted annual breast cancer mortality rates also decreased with increasing calendar period in nearly every patient group, by a factor of about three in oestrogen receptor positive disease and about two in oestrogen receptor negative disease. Mortality rates were highest during the five years after diagnosis before declining with each following five-year period.

There was still significant difference in mortality according to individual characteristics: <3% for 62.8% of women but taking into account age, oestrogen receptor type, and the number of lymph nodes involved, among other factors, for 4.6% the risk was ≥20%.

“[O]ur findings can be used to reassure most women treated for early breast cancer that they are likely to become long term survivors” as well as to identify cases with high mortality risk, the researchers wrote in The BMJ. They also note that the reduced mortality means that future randomised controlled trials, such as for new interventions, will need to be larger in order to have sufficient statistical power.

Categories : Ageing CancerTags :

Losing the Y Chromosome to Age Drives Bladder Cancers but Improves Immunotherapy

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Chromosomes. Credit: NIH

As men age, some of their cells lose their Y chromosome and this loss hampers the body’s ability to fight cancer, according to new research from Cedars-Sinai Cancer. The study, published in Nature, found that loss of the Y chromosome helps cancer cells evade the immune system, resulting in aggressive bladder cancer. Somehow, this also renders the disease more responsive to immune checkpoint inhibitors.

Based on their research, investigators are developing a test for loss of the Y chromosome in tumours with the goal of helping clinicians tailor immune checkpoint inhibitor treatment for male patients with bladder cancer.

“This study for the first time makes a connection that has never been made before between loss of the Y chromosome and the immune system’s response to cancer,” said corresponding author Dan Theodorescu, MD, PhD, who initiated the research. “We discovered that loss of the Y chromosome allows bladder cancer cells to elude the immune system and grow very aggressively.”

Lead collaborators on the study also included Johanna Schafer, a postdoctoral fellow, and Zihai Li, MD, PhD, medical oncologist and immunologist, both at The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute.

In men, loss of the Y chromosome has been observed in several cancer types, including 10%–40% of bladder cancers. Loss of the Y chromosome also has been associated with heart disease and Alzheimer’s disease.

The Y chromosome contains the blueprints for certain genes. Based on the way these genes are expressed in normal cells in the bladder lining, investigators developed a scoring system to measure loss of the Y chromosome in cancers.  

The investigators then reviewed data on two groups of men. One group had muscle invasive bladder cancer and had their bladders removed, but were not treated with an immune checkpoint inhibitor. The other group participated in a clinical trial and were treated with an immune checkpoint inhibitor. They found that patients with loss of the Y chromosome had poorer prognosis in the first group and much better overall survival rates in the latter.

To determine why this happens, investigators next compared growth rates of bladder cancer cells from laboratory mice.

Cancer cells were grown in vitro and not exposed to immune cells. The researchers also grew the diseased cells in mice that were missing T-cells. In both cases, tumours with and without the Y chromosome grew at the same rate.

In mice with intact immune systems, tumours lacking the Y chromosome grew at a much faster rate than did tumours with the intact Y chromosome.

“The fact that we only see a difference in growth rate when the immune system is in play is the key to the ‘loss-of-Y’ effect in bladder cancer,” Theodorescu said. “These results imply that when cells lose the Y chromosome, they exhaust T-cells. And without T-cells to fight the cancer, the tumor grows aggressively.”

Based on their results derived from human patients and laboratory mice, Theodorescu and his team also concluded that tumours missing the Y chromosome, while more aggressive, were also more vulnerable and responsive to immune checkpoint inhibitors. This therapy, one of the two mainstay bladder cancer treatments available to patients today, reverses T-cell exhaustion and allows the body’s immune system to fight the cancer.

“Fortunately, this aggressive cancer has an Achilles’ heel, in that it is more sensitive than cancers with an intact Y chromosome to immune checkpoint inhibitors,” said co-first author Hany Abdel-Hafiz, PhD, associate professor at Cedars-Sinai Cancer.

Preliminary data not yet published shows that loss of the Y chromosome also renders prostate cancers more aggressive, Theodorescu said.

“Our investigators postulate that loss of the Y chromosome is an adaptive strategy that tumour cells have developed to evade the immune system and survive in multiple organs,” said Shlomo Melmed, MB, ChB, dean of the Medical Faculty at Cedars-Sinai. “This exciting advance adds to our basic understanding of cancer biology and could have far-reaching implications for cancer treatment going forward.”

Further work is needed to help investigators understand the genetic connection between loss of the Y chromosome and T-cell exhaustion.

“If we could understand those mechanics, we could prevent T-cell exhaustion,” Theodorescu said. “T-cell exhaustion can be partially reversed with checkpoint inhibitors, but if we could stop it from happening in the first place, there is much potential to improve outcomes for patients.”

While women do not have a Y chromosome, Theodorescu said these findings could have implications for them as well. The Y chromosome contains a set of related genes, called paralogue genes, on the X chromosome, and these might play a role in both women and in men. Additional research is needed to determine what that role might be.

“Awareness of the significance of Y chromosome loss will stimulate discussions about the importance of considering sex as a variable in all scientific research in human biology,” Theodorescu said. “The fundamental new knowledge we provide here may explain why certain cancers are worse in either men or women, and how best to treat them. It also illustrates that the Y chromosome does more than determine human biologic sex.”

Source: Cedars-Sinai Medical Center

Categories : CancerTags :

Game-changing Therapy Targets Colon Cancer that has Spread to the Liver

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Source: CC0

Physicians at Cedars-Sinai Cancer are now using a unique therapy, called hepatic artery infusion (HAI) pump chemotherapy, that offers hope to colorectal cancer patients whose disease has spread and who now have inoperable liver tumours. The system, which was developed over two decades ago, is only now being adopted more widely, also spares the rest of the body from much of the chemotherapy drugs’ toxicity.

“Many of these patients are not candidates for curative surgery and we now have a meaningful option for treating them,” said Cristina Ferrone, MD, chair of the Department of Surgery at Cedars-Sinai and a specialist in the care of patients with complex hepato-pancreato-biliary disorders. “This therapy has been shown to extend both life and quality of life.”

Colorectal cancer is the fourth-leading cause of cancer-related death in the US. In as many as 25% of patients diagnosed with the disease, the cancer spreads to the liver, where it can be difficult to treat. However, more than half of patients receiving hepatic artery infusion pump therapy go on to receive curative surgery, studies have shown.

Cedars-Sinai Cancer and associate professor of Surgery at Cedars-Sinai, sat down with the Cedars-Sinai Newsroom to explain this lifesaving therapy.

How do the pumps work?

We surgically place the pump underneath the skin, outside of the abdominal cavity, and it is attached to tubing that enters the abdominal cavity and goes into the gastroduodenal artery. That artery feeds into the hepatic artery, which supplies blood to the liver. During surgery, we block blood flow from the gastroduodenal artery from going into portions of the small intestine so that the therapy flows only to the liver.

The pump has a soft centre, allowing its internal reservoir to be filled through the skin via a syringe. After surgery, the patient comes in every two weeks and we refill the pump, which then allows the chemotherapy drug to flow directly into the liver via the arterial supply.

Which patients are likely to benefit from hepatic artery infusion pump therapy?

This therapy is designed for patients, based on the distribution of the metastatic disease (where are the tumours and how many), for whom curative surgery is not an option at the time of diagnosis. The best we had been able to offer these patients was lifelong chemotherapy that had potential systemic toxicities, and that never quite reduced their tumour size to the point that we could surgically remove it. This therapy offers an additional option for liver-directed therapy that can potentially make patients candidates for surgery by specifically targeting the liver disease.

What are the advantages of the hepatic artery infusion pump over traditional chemotherapy delivery?

A majority of these tumours derive their blood supply from the hepatic arterial system, and delivering chemotherapy to the tumours through the hepatic arterial system allows us to give higher doses of specific chemotherapeutic agents without exposing the patient to their systemic toxicities. Data shows that up to 60% of appropriately selected patients receiving hepatic artery infusion pump chemotherapy were then able to receive curative surgery. Patients can often continue receiving systemic chemotherapy in combination with hepatic artery infusion pump chemotherapy.

Are hepatic artery infusion pumps used to treat other types of liver cancer?

Some patients with cholangiocarcinoma are currently treated with HAI pumps, but this is not yet standard of care. Colon cancer is the second most common cancer, and colon cancer that has metastasized to the liver affects a significant number of patients. And we have seen good outcomes with those patients. Other types of cancers that metastasise to the liver are significantly more challenging to treat, and thus far, we don’t think this therapy will benefit those patients.

Is this a new therapy?

Hepatic artery infusion pumps have actually been around for about 25 to 30 years, but until quite recently only a few medical centres were using them. But more and more centres are realising that this therapy can truly benefit patients, and it is becoming more widely available.

Source: Cedars-Sinai Medical Center

Categories : Cancer Lab Tests and ImagingTags :

Gliomas Have Folates Receptors That Could be Targeted for Imaging

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University of Turku researchers have discovered that gliomas contain increased amount of folate receptor expression relative to adjacent brain tissue. This discovery is a new and significant finding in the field, which could allow folate-based radiopharmaceuticals can be used in positron emission tomography (PET) imaging to detect folate receptors in gliomas.

This phenomenon, which is described in Frontiers in Immunology, has been observed in both experimental models and human tumour samples.

“Prior to this discovery, the presence of folate receptors and their increased presence in gliomas had not been recognised, and thus they have not yet been used for imaging nor treatment purposes,” summarises Doctoral Researcher Maxwell Miner from the Turku PET Centre at the University of Turku in Finland.

According to research group leader and InFLAMES PI Professor Anne Roivainen this presents an especially exciting target for potential future treatments.

“Our results show an average of 100-fold increase in folate-based radiopharmaceutical accumulation in glioma tissue versus that of adjacent healthy brain tissue,” says Professor Roivainen.

Urgent need for new chemotherapy treatments

Glioma brain tumours originate from the non-neuronal glial cells in the brain, which outnumber neurons in quantity. Gliomas comprise numerous subgroups, with even a high degree of morphological and receptor variability within a single cancerous lesion.

This exceptional cellular heterogeneity can make treatment difficult. There is an urgent need for new chemotherapy treatments particularly for the most malignant brain cancers as they often grow in an infiltrative web-like manner on their periphery making distinguishing the boundaries between glioma and non-glioma difficult. The researchers at the Turku PET Centre hope that this recent discovery will lead to further investigation into folate-targeted brain tumour detection and treatment.

Source: University of Turku

Categories : CancerTags :

How Accurate is Supplemental Ultrasound in Breast Cancer Screening Failures?

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Dense breast tissue, which contains a higher proportion of fibrous tissue than fat, is a risk factor for breast cancer and also makes it more difficult to identify cancer on a mammogram. Many US states have enacted laws that require women with dense breasts to be notified after a mammogram, so that they can choose to undergo supplemental ultrasound screening to improve cancer detection. A recent study published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society, evaluated the results of such additional screening to determine its benefits and harms to patients.

Although supplemental ultrasound screening may detect breast cancers missed by mammography, it requires additional imaging and may lead to unnecessary breast biopsies among women who do not have breast cancer. Therefore, it is important to use supplemental ultrasound only in women at high risk of mammography screening failure – in other words, women who develop breast cancer after a mammogram shows no signs of malignancy.

Brian Sprague, PhD, of the University of Vermont Cancer Center, and his colleagues evaluated 38 166 supplemental ultrasounds and 825 360 screening mammograms without supplemental ultrasounds during 2014–2020 at 32 US imaging facilities within three regional registries of the Breast Cancer Surveillance Consortium.

The team found that 95.3% of supplemental ultrasounds were performed in women with dense breasts. In comparison, 41.8% of mammograms without additional screening were performed in women with dense breasts.

Among women with dense breasts, a high risk of interval invasive breast cancer was present in 23.7% of women who underwent ultrasounds, compared with 18.5% of women who had mammograms without additional imaging.

The findings indicate that ultrasound screening was highly targeted to women with dense breasts, but only a modest proportion of these women were at high risk of mammography screening failure. A similar proportion of women who received only mammograms were at high risk of mammography screening failure.

“Among women with dense breasts, there was very little targeting of ultrasound screening to women who were at the highest risk of a mammography screening failure. Rather, women with dense breasts undergoing ultrasound screening had similar risk profiles to women undergoing mammography screening alone,” said Dr Sprague. “In other words, many women at low risk of breast cancer despite having dense breasts underwent ultrasound screening, while many other women at high risk of breast cancer underwent mammography alone with no supplemental screening.”

Clinicians can consider other breast cancer risk factors beyond breast density to identify women who may be appropriate for supplemental ultrasound screening. Publicly available risk calculators from the Breast Cancer Surveillance Consortium are available that also consider age, family history, and other factors (https://www.bcsc-research.org/tools).

Source: Wiley

Categories : Cancer Cardiovascular DiseaseTags :

Some Antihypertensives might Boost the Effectiveness of Cancer Immunotherapy

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A study reported in the latest issue of Nature has shown that some molecules previously used to treat hypertension might also help the immune system to better target cancer cells. The researchers believe that these findings could eventually be applied to significantly improve the effectiveness and applicability of cancer immunotherapy.

“Immunotherapy today can effectively fight only 30% to 40% of cancers,” said Benoît Van den Eynde, at the Ludwig Institute for Cancer Research, co-director of the de Duve Institute and professor of Tumour Immunology at the University of Oxford. “Many cancers are resistant, largely because their T lymphocytes are not reactive enough. We discovered that drugs once used to treat hypertension could have a very interesting effect in combating these forms of immunotherapy-resistant cancers.”

T lymphocytes are active components in the immune system, recognising and destroying cells that appear foreign. Cancer cells, however, are not foreign and are therefore often not recognised and attacked by T lymphocytes. But about thirty years ago, Thierry Boon and his colleagues at the former Brussels Branch of the Ludwig Institute for Cancer Research at the de Duve Institute discovered specific markers on the surface of cancer cells – tumour antigens – that can be recognised by T cells that then destroy the cancerous cells.

This work paved the way for cancer immunotherapy, a treatment approach that helps T cells destroy cancerous cells. Thanks to T cells’ specificity and memory of tumour antigens, immunotherapy makes it possible to treat advanced cancers with some success. It is now used worldwide. However, such therapies are not equally effective in all patients or against all types of cancer.

In the current study, a team led by Jingjing Zhu in Van den Eynde’s laboratory shows that anti-hypertensive drug-molecules known as α2-adrenergic receptor (α2AR) agonists also influence the behaviour of macrophages. While doing that job, macrophages also alert T cells of any abnormalities they encounter, presenting suspicious antigens to the cells to trigger a possible immune response.

Zhu, Van den Eynde and colleagues discovered that alongside their known hypotensive and anaesthetic effects, α2AR agonists can also stimulate macrophages in their role as sentinels, making T cells more reactive and more effective at rejecting cancer cells. The effect extended, most notably, to cancer models that are resistant to standard immunotherapy. This suggests the new approach could boost the efficacy of clinical immunotherapy, even for the many types of cancer that are largely unresponsive to such interventions.

These findings also present a rationale for the development of new molecules that might be used in combination with immunotherapy to improve its efficacy.

“One could imagine using existing blood pressure-lowering drugs,” said Van den Eynde. “But that would be quite risky, owing to the undesired effects and the toxicity of these drugs at the necessary doses. Another approach would be to develop new molecules that would act in the same way on macrophages but would not have the unwanted toxic effects. We have already made significant progress in this direction.”

Source: Ludwig Cancer Research

Categories : CancerTags :

Vorasidenib Extends Progression-free Survival in Glioma Subtype

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In a study published in the New England Journal of Medicine, scientists report that a new targeted therapy drug can extend progression-free survival for a subtype of glioma. The finding suggests a possible new treatment option for people with the slow-growing but deadly brain tumour.

The team, co-led by UCLA, found the drug vorasidenib more than doubled progression-free survival in people with recurrent grade 2 glioma with IDH1 and IDH2 mutations. Compared with placebo, those who took vorasidenib went for nearly 17 more months without their cancer worsening, delaying the time before they needed to begin chemotherapy and radiation.

The type of glioma studied in the paper, recurrent grade 2 glioma with IDH1 and IDH2 mutations, tends to affect younger people, often those in their 30s. The current standard treatment, a combination of radiation and chemotherapy, can cause neurological deficits that make it hard for patients in an often challenging and busy stage of life.

UCLA professor of neuro-oncology Dr Timothy Cloughesy, co-senior author of the study, said that the availability of a treatment that enables patients to go for longer periods of time between chemotherapy and radiation treatments could have a major impact.

“We’re always concerned about the delayed effects of radiation,” said Cloughesy. “Having the ability to hold off on getting radiation therapy to the brain with an effective therapy is really critical and very meaningful to this population of patients.”

Vorasidenib is a dual inhibitor of mutant IDH1/2, meaning that it prevents the formation and accumulation of the onco-metabolite 2-Hydroxyglutarate, or 2-HG, that occurs when genetically altered versions of two enzymes, IDH1 and IDH2, are present in a tumour. 2-HG is thought to be responsible for the formation and maintenance of IDH-mutant gliomas.

The study is also the first clinical trial to analyse a targeted therapy drug specifically developed to treat brain cancer. Targeted therapies focus on specific molecules that are involved in cancer cell growth and metastasis. Unlike chemotherapy and other therapies that can affect both cancerous and healthy cells, targeted therapies only attack cancer cells with the mutated target while sparing normal cells.

While there has been great progress in using targeted therapies to treat many types of cancer, the difficulty of crossing the blood-brain barrier makes developing targeted therapies for brain tumours challenging. Vorasidenib is a brain-penetrant inhibitor, allowing it to cross the blood-brain barrier.

The study involved 331 people aged 12 and older who had been diagnosed with recurrent grade 2 glioma with the IDH1 and IDH2 mutations and who had undergone brain tumour surgery. From that group, 168 were randomised to vorasidenib and 163 to placebo.

Among those who received vorasidenib, the disease did not progress for an average of 27.7 months, significantly longer than the 11.1 months for those who received the placebo. And among those who received vorasidenib, 85.6% went for 18 months before their next treatment, while 83.4% went for 24 months between treatments.

The disease progressed in just 28% of people receiving v orasidenib, compared to 54% of those receiving placebos. And as of September 2022, which was 30 months after the study began, 72% of patients who were in the vorasidenib group were still taking the drug and their disease had not progressed.

For patients who were originally in the placebo group whose cancer began to progress during the study, doctors permitted a switch to vorasidenib. The researchers observed limited adverse side effects from vorasidenib. “This is the first targeted treatment that shows unequivocal efficacy in this population and is precedent-setting for this disease,” Cloughesy said.

Source: University of California – Los Angeles Health Sciences