Tag: cancer

Many Young People with Cancer Experiencing Distress in the Pandemic

Photo by Sydney Sims on Unsplash

A new study has reported that many adolescents and young adults with cancer are suffering high psychological distress during the COVID pandemic. During the pandemic, adolescents and young adults with cancer had an 85% higher odds of experiencing psychological distress compared with a similar group surveyed in 2018.

For the study, which was published in Psycho-Oncology, 805 individuals in Canada who were diagnosed with cancer between 15 and 39 years of age completed an online survey.  

More than two‐thirds of the group (68.0%) experienced high psychological distress. Additionally, those whose employment had been disrupted during the pandemic and those with blood cancer were more likely to experience high psychological distress, while those who were older and those with a personal income in 2020 that was less than $40 000 tended to have lower distress.  

The survey revealed overarching themes of pandemic experiences that included inferior quality of life, impairment of cancer care, COVID–related concerns, and extreme social isolation.  

“The pandemic has adversely impacted the mental health of adolescents and young adults with cancer,” said senior author Sapna Oberoi, MBBS, MD, DM, of the University of Manitoba. “The findings of this study underscore the importance of providing enhanced and tailored interventions to combat psychological distress among these patients. Cancer organisations and policymakers must prioritise mental health supports for adolescents and young adults with cancer to optimise their health outcomes and quality of life.”

Source: Wiley

Why Cancer Cells Linger to Create Metastatic Cancer

Colon cancer cells. Source: National Cancer Institute on Unsplash

A major mystery in cancer research has been solved: How cancer cells remain dormant for years after leaving a tumour before awakening to create metastatic cancer.

According to findings by Mount Sinai researchers which were reported in Nature Cancer, the cells remain quiet by secreting a type of collagen, called type III collagen, in the environment around themselves, and only turn malignant once the level of collagen tapers off. The researchers found that by enriching the environment around the cells with this collagen, they could force the cells to remain in a dormant state and prevent tumour recurrence.

“Our findings have potential clinical implications and may lead to a novel biomarker to predict tumour recurrences, as well as a therapeutic intervention to reduce local and distant relapses,” said senior author Jose Javier Bravo-Cordero, PhD, Associate Professor of Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at Mount Sinai. “This intervention aimed at preventing the awakening of dormant cells has been suggested as a therapeutic strategy to prevent metastatic outgrowth. As the biology of tumour dormancy gets uncovered and new specific drugs are developed, a combination of dormancy-inducing treatments with therapies that specifically target dormant cells will ultimately prevent local recurrence and metastasis and pave the way to cancer remission.”

Most cancer deaths result from metastases, which can occur several years after removal of a tumour. Previous work looked at how dispersed tumour cells awaken from dormancy; this new work showed how the cells remain dormant.

The study used high-resolution imaging techniques, including intravital two-photon microscopy, a technology that allows the visualisation of dormant cells in their environment in real time in a living animal. This technology allowed the researchers to track dormant tumour cells in mouse models using cancer cell lines. By using this technology, the researchers were able to visualise the changes in the architecture of the extracellular matrix as tumour cells became dormant and how it changed when these cells awoke.

The researchers demonstrated that an abundance of the collagen could potentially be used as a predictor of tumour recurrence and metastasis. In the mouse models, when type III collagen was increased around cancer cells that had left a tumour, cancer progression was interrupted and the disseminated cells were forced into a dormant state. Similar to wound treatment, in which collagen scaffolds have been proposed to treat complex skin wounds, this study suggests that by enriching the tumour microenvironment in type III collagen, metastasis may be prevented by sending tumour cells into a dormant state.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

How Epithelial Cells Kick out Precancerous Neighbours

Melanoma cells. Source: National Cancer Institute.

Researchers have discovered the mechanism behind how normal epithelial cells push out precancerous ones present in the epithelium with  ‘cell competition’. Researchers have unravelled the interactions and cellular pathways leading to this extrusion, allowing them to identify a candidate for a therapeutic target for future cancer prevention research.

Recent studies have shown that the human body has defence mechanisms run by non-immune epithelial cells. These epithelial cells can recognise and extrude neighbouring precancerous cells from the epithelium, known as cell competition. This form of immune-like surveillance has garnered attention in recent years based on its potential for future immune-like therapeutic targets for cancer preventive treatment. However, it is still unknown what kind of ligand-receptor interactions are involved in the recognition of precancerous cells by normal epithelial cells.

Discussing the study, Professor Takeshi Maruyama, an Associate Professor at the Waseda Institute for Advanced Study at Waseda University, who led the research group, says, “During the process of cell competition, normal epithelial cells can be primed by contact with precancerous cells. However, it was previously unclear how neighbouring normal epithelial cells recognise precancerous cells to eliminate them.”

In this work, the researchers identified a plasma membrane protein, leukocyte immunoglobulin-like receptor B3 (LILRB3). AltR/LILRB3 interacts with major histocompatibility complex class I (MHC class I) that is expressed on precancerous epithelial cells.

MHC class I-AltR/LILRB3 interaction causes the activation of AltR/LILRB3, which triggers an intracellular SHP2–ROCK2 pathway. This SHP2–ROCK2 pathway leads to the “accumulation of cytoskeletal components”, creating a mechanical force to extrude precancerous cells, in the normal epithelial cells at the boundary with precancerous cells. This pushes the precancerous cells out of the epithelium to eliminate them from the body.

However, this occurs independently of natural killer or CD8+ T cell-mediated immune responses. “Our study describes a new immune-like mechanism by non-immune epithelial cells to suppress tumorigenesis,” said Prof Maruyama.

The researchers hope that these findings can be applied to cancer treatment. “The recombinant MHC-I-α3 protein used in this study enhances the elimination of precancerous cells and suppresses the formation of tumours and precancerous lesions,” added Prof Maruyama. “We hope that this biomolecule would contribute to a therapeutic candidate for cancer prevention by the elimination of precancerous cells.”

Source: Waseda University

Synthetic Progestogen in Utero Leads to Doubled Cancer Rate in Offspring

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In utero exposure to a synthetic progestogen used to prevent miscarriage can lead to an increased risk of developing cancer, according to a new study.

The study by researchers at The University of Texas Health Science Center at Houston (UTHealth Houston) was published in the American Journal of Obstetrics and Gynecology.

The drug, 17α-hydroxyprogesterone caproate (17-OHPC), is a synthetic progestogen frequently used by women in the 1950s and 1960s, and is still prescribed today to women to help prevent preterm birth. Progesterone helps the uterus grow during pregnancy and prevents early contractions that may lead to miscarriage.

“Children who were born to women who received the drug during pregnancy have double the rate of cancer across their lifetime compared to children born to women who did not take this drug,” said the study’s lead author, Caitlin C. Murphy, PhD, MPH, associate professor in the Department of Health Promotion and Behavioral Sciences at UTHealth School of Public Health in Houston. “We have seen cancers like colorectal cancer, pancreatic cancer, thyroid cancer, and many others increasing in people born in and after the 1960s, and no one really knows why.”

Researchers reviewed data from the Kaiser Foundation Health Plan on women who received prenatal care between June 1959 and June 1967, and the California Cancer Registry, which traced cancer in offspring through 2019.

Out of more than 18 751 live births, researchers discovered 1008 cancer diagnoses were made in offspring ages 0 to 58 years. Additionally, a total of 234 offspring were exposed to 17-OHPC during pregnancy. Offspring exposed in utero had cancer detected in adulthood at more than twice the rate of of those unexposed: 65% of cancers occurred in adults younger than 50.

“Our findings suggest taking this drug during pregnancy can disrupt early development, which may increase risk of cancer decades later,” Murphy said “With this drug, we are seeing the effects of a synthetic hormone. Things that happened to us in the womb, or exposures in utero, are important risk factors for developing cancer many decades after we’re born.”

A new randomised trial shows there is no benefit of taking 17-OHPC, and that it does not reduce the risk of preterm birth, according to Murphy.

The U.S. Food and Drug Administration proposed in October 2020 that this particular drug be withdrawn from the market.

Source: University of Texas Health Science Center at Houston

An Inspiration Led to Understanding Metformin’s Anti-tumour Effect

Scientists report that metformin, used to treat type 2 diabetes mellitus, induces activation and proliferation of tumor-targeting CD8+ T-lymphocytes (CD8TIL), via mechanisms that involve the generation of reactive oxygen species in mitochondria of CD8TIL and an increase in glycolysis. Credit: Heiichiro Udono from Okayama University

Researchers in Japan have elucidated how the antidiabetic drug metformin exerts an anti-tumour effect as well.

Certain drugs like metformin have recently been found to have anti-cancer properties. Metformin appears to bolster anti-tumour immunity but the underlying immunological mechanisms were a mystery. With all the permutations and combinations of cancer, a blanket, yet targeted therapy would be ideal. 

Japanese scientists led by Professor Heiichiro Udono from Okayama University thus decided to address this oncological research question. In their recent study, they looked at how a specific subset of immune cells, called CD8+ infiltrating T-lymphocytes (CD8TIL), which specifically attack tumor cells, behaved in response to metformin. Their findings have been published as a research article in Journal for ImmunoTherapy of Cancer.

Interestingly, Prof. Udono almost gave up on his anti-cancer pursuits, when he lost his own father to cancer. However, a bolt of inspiration came at a conference: “Nearly 10 years ago, a switch turned on in my head when I attended a Keystone Symposia discussing cancer, and hypoxia, held in Banff, Alberta. I realised that we had missed addressing Warburg effect, an effect which bolsters the growth of cancer, in our previous research. So, reverting Warburg effect to normal metabolic profile in cancers became a topic that got me thinking. Surprisingly, I got a hint from the same conference that metformin may aid cancer immunity. So, we got to work!”

Prof Udono and his team got to work, meticulously conducting a series of experiments on cancer cell lines, and ‘knockout gene’ mice, searching for possible biomolecules that result in metformin-dependent anti-tumour immunity. They probed the intracellular mechanisms in CD8TIL, when exposed to metformin, and assessed different biomarkers for growth. Given that CD8TIL produces proteins called interferons to attack cancer cells, they also assessed corresponding levels.

Accordingly, the scientists found that metformin causes the generation of reactive oxygen species in the mitochondria of CD8TIL (mtROS) and increases glycolysis. They also found that mtROS activated growth pathways in CD8TIL, allowing these cells to proliferate. Notably, this is achieved through a transcription factor involved in anti-oxidative stress response, called Nrf. Though metformin did not directly cause apoptosis, ‘cell suicide’ in tumours, it did cause CD8TIL to secrete interferon-ɣ to alter the tumour microenvironment in favour death of tumour cells.

Summing up the findings, Prof. Udono said: “More than anything else, our study provides the knowledge that we can ourselves protect our body from cancer. We hope that this understanding will result in not only the reduction of cancer incidence and improve treatment, but also will help prolong our life.”

The researchers also added that these findings strongly suggest the possibility of using metformin as a drug to strengthen anti-tumour immunity in patients with cancer. The findings appear in the Journal for ImmunoTherapy of Cancer.

Source: EurekAlert!

Telemedicine Popular Among People with Cancer Undergoing Radiotherapy

Source: Pixabay

Researchers reviewing patient surveys before and during the COVID pandemic found that nearly half preferred telemedicine and that general patient satisfaction scores were equally high for both video conferencing and office visits.

The study, published in the Journal of the National Comprehensive Cancer Network, assessed patient satisfaction and preferences for telemedicine. It found that 45% of people with cancer preferred telemedicine, while 34% preferred office visits, and 21% had no preference.

The researchers reviewed survey responses from 1077 radiation oncology patients across seven centres, with questionnaires based on office and telemedicine visits between December 2019 and June 2020. In terms of patient satisfaction, most reported either no difference or improvement with telemedicine overall (91%) compared to office visits, with similar results for their confidence in their physician (90%), understanding their treatment plans (88%), and confidence their cancer will be treated appropriately (87%).

Co-lead author Narek Shaverdian, MD, MSK Department of Radiation Oncology said: “These findings provide some evidence that there is a role for telemedicine beyond the COVID-19 pandemic and that it can be a particularly useful tool for certain patients – especially those who may have challenges coming on-site for an appointment. Giving patients flexibility and options by being able to see them both in-person and through telemedicine can improve access to care.”

Notably, two-thirds of respondents considered telemedicine to be a superior option when it came to treatment-related costs, such as travel and lost wages.

Co-lead author Erin F. Gillespie, MD, MSK Department of Radiation Oncology said, “An individual visit to the physician’s office can be costly—including transportation, parking, and time off from other activities. Telemedicine takes away most of this cost and inconvenience, and could therefore reduce the overall burden of engaging with the healthcare system. Also, the ability for family and friends to join the conversation from any location can be game-changing.”

The researchers found patient responses varied significantly between video conferencing versus audio. Patients who had telephone-only appointments were more likely to say they thought they would benefit more from an in-person visit.

“Telemedicine can be a resource to increase access to care, but only if patients have and can use these video capabilities,” said Dr. Shaverdian. “There is so much that you learn just by seeing a patient and using visual cues to guide a discussion. A voice-only encounter with a patient you’ve never met before is challenging.”

“Digital tools like telemedicine have the unfortunate potential consequence of paradoxically increasing disparities in access to care,” noted Dr. Gillespie. “But the counter to that is there will be some disadvantaged patients that would not have accessed the system at all, either due to technologic barriers or travel time, and now can connect at least by phone, which is an important and positive change.”

Source: National Comprehensive Cancer Network

Many Breast Cancer Patients Don’t Discuss Cannabis Use with Docs

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About half of US adults with breast cancer use cannabis as an adjunct to cancer treatment for symptom and side effect management. However, most don’t discuss their use of cannabis with their physicians, according to a new study.

Pain, fatigue, nausea, and other difficulties often arise from cancer and its treatment, and some patients turn to cannabis for relief of their symptoms. However, many physicians feel that they lack the necessary knowledge to discuss cannabis with their patients. Such knowledge is especially important now that cannabis use is becoming more widespread.

In a study published in CANCER, researchers reported the results of an anonymous online survey to examine cannabis use among adults who were diagnosed with breast cancer within five years and were members of the Breastcancer.org and Healthline.com online health communities.

The findings revealed that:

  • Of the 612 participants, 42% reported using cannabis for relief of symptoms, including pain, insomnia, anxiety, stress, and nausea/vomiting. Among those who used cannabis, 75% reported that it was extremely or very helpful at relieving their symptoms.
  • Nearly half (49%) of participants who used cannabis believed that medical cannabis can be used to treat cancer itself; however, its effectiveness against cancer is unclear.
  • Among those using cannabis, 79% had used it during treatment, which included systemic therapies, radiation, and surgery.
  • Participants reported using a wide range of different cannabis products known to vary in quality and purity.
  • Half of participants sought information on medical cannabis, and websites and other patients were ranked as the most helpful sources of information. Physicians ranked low on the list.
  • Among those who sought information on cannabis use for medical purposes, most were unsatisfied with the information they received.
  • Most participants believed cannabis products to be safe and were unaware that the safety of many products is untested.

“Our study highlights an important opportunity for providers to initiate informed conversations about medical cannabis with their patients, as the evidence shows that many are using medical cannabis without our knowledge or guidance,” said lead author Marisa Weiss, MD, of Breastcancer.org and Lankenau Medical Center near Philadelphia, Pennsylvania. “Not knowing whether or not our cancer patients are using cannabis is a major blind spot in our ability to provide optimal care, and as healthcare providers, we need to do a better job of initiating informed conversations about medical cannabis with our patients to make sure their symptoms and side effects are being adequately managed while minimising the risk of potential adverse effects, treatment interactions, or non-adherence to standard treatments due to misinformation about the use of medical cannabis to treat cancer.”

Dr Weiss added that patients should never use cannabis as an alternative to standard cancer treatment, and clinicians should inform patients about the safe and effective use of cannabis as an adjunct to their cancer treatment plan.

Source: Wiley

COVID Vaccines less Effective in Patients Undergoing Chemotherapy

Photo by National Cancer Institute on Unsplash

New research has found that patients undergoing active chemotherapy had a lower immune response to two doses of the COVID vaccine, although a third dose increased response.

“We wanted to make sure we understand the level of protection the COVID vaccines are offering our cancer patients, especially as restrictions were being eased and more contagious variants were starting to spread,” said Rachna Shroff, MD, MS, University of Arizona Health Sciences.

To find out, Dr Shroff and colleagues looked at 53 Cancer Center patients on immunosuppressive active cancer therapy, such as chemotherapy. They compared the immune response following the first and second dose of the Pfizer-BioNTech COVID vaccine with that of 50 healthy adults. 

After two vaccine doses, most of the cancer patients showed some immune response to the vaccine in that they had produced antibodies for SARS-CoV-2.

“We were pleasantly surprised,” said Deepta Bhattacharya, PhD, professor of immunobiology in the College of Medicine – Tucson. “We looked at antibodies, B cells and T cells, which make up the body’s defense system, and found the vaccine is likely to be at least partially protective for most people on chemotherapy.”

However, this  immune response was much lower than in healthy adults, and a few of the patients had no response to the COVID  vaccine. This translates to less protection against SARS-CoV-2, especially the now-dominant Delta variant.

Twenty patients returned for a third shot, which boosted the immune response for most. The overall group immune response after the third shot reached levels similar to those of people who were not on chemotherapy after two doses.

The results were published in Nature Medicine.

Source: University of Arizona Health Sciences

SSRI Antidepressants Could be Used To Fight Cancer

Natural killer (NK) cells target a cancel cell for destruction. Credit: NCI

Long used to treat depression, selective serotonin reuptake inhibitors (SSRIs) could help improve modern cancer treatments.

In mouse experiments, they slowed the growth of pancreatic and colon cancers, and when combined with immunotherapy, they even halted cancer growth long-term. In some cases the tumours disappeared completely. The researchers’ findings will now be tested in human clinical trials.

The neurotransmitter serotonin, known as the happiness molecule, has many other functions and is mostly found outside the brain, stored in blood platelets. Serotonin reuptake inhibitors (SSRIs), which are used to treat depression, increase serotonin levels in the brain but reduce serotonin in platelets.

Serotonin was already known to be involved  in carcinogenesis. Until now, however, the underlying mechanisms had remained obscure. Now, researchers at the University of Zurich (UZH) and University Hospital Zurich (USZ) have shown that SSRIs or other drugs that lower peripheral serotonin levels can also slow cancer growth in mice.

Pierre-Alain Clavien, Director, Department of Surgery and Transplantation, University of Zurich, said: “Drugs that are already approved for clinical use as antidepressants could help improve treatment of hitherto incurable pancreatic and colorectal cancers.”

Although recent years have seen new, effective treatments such as targeted antibodies or immunotherapies, most patients with advanced-stage abdominal tumours such as colon or pancreatic cancer die within a few years of diagnosis. Tumour cells eventually become resistant to the drugs and are no longer recognised by the immune system. Now, the researchers have discovered the role serotonin plays in this tumour cell resistance mechanism.

Cancer cells use serotonin to boost production of an immunoinhibitory molecule, PD-L1, which binds to killer T cells, rendering them dysfunctional. The cancer cells thus escape destruction by the immune system. In mouse models, the researchers were able to show that SSRIs or peripheral serotonin synthesis inhibitors prevent this mechanism. “This class of antidepressants and other serotonin blockers cause immune cells to recognise and efficiently eliminate tumor cells again. This slowed the growth of colon and pancreatic cancers in the mice,” Clavien said.
PD-L1, via which serotonin exerts its effect, is also the target of modern immunotherapies, also called immune checkpoint inhibitors. The researchers then tested a dual treatment approach in mice: immunotherapy, which increases the activity of killer T cells, was combined with drugs that reduce peripheral serotonin. Cancer growth was suppressed in the animal models in the long term, and in some mice, the tumours disappeared completely.

“Our results provide hope for cancer patients, as the drugs used are already approved for clinical use. Testing such drug combinations on cancer patients in clinical trials can be fast-forwarded due to the known safety and efficacy of the drugs,” said Clavien.

Source: University of Zurich

Oxford-AstraZeneca Vaccine Tech Tapped to Treat Cancer

Source: National Cancer Institute on Unsplash

The Oxford-AstraZeneca vaccine’s success against SARS-CoV-2 has prompted scientists to develop a vaccine for cancer, using Oxford’s viral vector vaccine technology.

When tested in mouse tumour models, the two-dose therapeutic cancer vaccine increased the numbers of anti-tumour T cells infiltrating the tumours and improved the efficacy of cancer immunotherapy. Compared to immunotherapy alone, combination with the vaccine resulted in a greater reduction in tumour size and improved survival.

The study, which was done by Professor Benoit Van den Eynde’s group at the Ludwig Institute for Cancer Research, University of Oxford in collaboration with co-authors Professor Adrian Hill and Dr Irina Redchenko at the University’s Jenner Institute, has been published in the Journal for ImmunoTherapy of Cancer.

Cancer immunotherapy has improved outcomes for some cancer patients. Anti-PD-1 immunotherapy works by unleashing anti-tumour T cells to allow them to kill cancer cells. However, in the majority of cancer patients, anti-PD-1 therapy is still ineffective .

One reason for the poor efficacy of anti-PD-1 cancer therapy is that some patients have low levels of anti-tumour T cells. Oxford’s vaccine technology generates strong CD8+ T cell responses, which are necessary for strong anti-tumour effects.

The team developed a two-dose therapeutic cancer vaccine with different prime and boost viral vectors, one of which is the same as the vector in the Oxford-AstraZeneca COVID vaccine. In order to create a vaccine treatment that specifically targets cancer cells, the vaccine was designed to target two MAGE-type proteins found on the surface of many types of cancer cells.

Preclinical experiments in mouse tumour models demonstrated that the cancer vaccine increased the levels of tumour-infiltrating CD8+ T cells and enhanced the response to anti-PD-1 immunotherapy. The combined vaccine and anti-PD-1 treatment resulted in a greater reduction in tumour size and improved the survival of the mice compared to anti-PD-1 therapy alone.

Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford, said: “We knew from our previous research that MAGE-type proteins act like red flags on the surface of cancer cells to attract immune cells that destroy tumours.

“MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumour types. This broadens the potential benefit of this approach to people with many different types of cancer.

“Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side-effects caused by the immune system attacking healthy cells.”

Human trials in 80 patients with non-small cell lung cancer will be launched later this year.

Adrian Hill, Lakshmi Mittal and Family Professorship of Vaccinology and Director of the Jenner Institute, University of Oxford, said: “This new vaccine platform has the potential to revolutionise cancer treatment. The forthcoming trial in non-small cell lung cancer follows a Phase 2a trial of a similar cancer vaccine in prostate cancer undertaken by the University of Oxford that is showing promising results.

“Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumours and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer.”

Source: Oxford University