The timing of immunotherapy administration influences treatment effectiveness, with morning treatment associated with significantly better survival outcomes, according to new real-world data presented at the EAHP Congress in Barcelona.

Researchers from six hospitals across the Balearic Islands in Spain analysed nearly 9,000 immunotherapy infusions given to 1,175 patients between January 2021 and June 2025. The study examined whether the time of day at which checkpoint inhibitors — pembrolizumab, nivolumab, and atezolizumab — were administered affected overall survival in patients with metastatic cancer.

Patients were divided into two groups based on whether fewer or more than 50% of their doses were given in the afternoon (after 3 pm). The majority of administrations (62.3%) took place in the morning. The cohort was predominantly male (66.4%), with a mean age of 66 years and the most common diagnoses were non-small-cell lung cancer (54%) and small-cell lung cancer (12.7%).

The survival difference between the two groups was striking. Overall survival was not reached in the morning group, compared to just 28.6 months in the afternoon group. The hazard ratio of 0.64 (95% CI 0.53–0.78; p<0.0001) indicates that patients receiving predominantly morning infusions had a 36% lower risk of death during the follow-up period.

These findings align with the emerging field of chronotherapy — the idea that the body’s circadian rhythms influence how well treatments work. Immune function fluctuates throughout the day, and morning administration may coincide with peak immunological activity, enhancing the effectiveness of checkpoint inhibitors.

The authors conclude that where scheduling allows, morning administration of immunotherapy should be prioritised to optimise patient outcomes — a simple, cost-neutral change with potentially significant survival benefits.

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But there are few evidence-based interventions to help this age group problem-solve and reduce stress. To address the gap, Rutgers University researchers tested the efficacy of Bright IDEAS, a problem-solving skills training intervention based on cognitive-behavioral therapy, in reducing depression and anxiety and improving their overall health-related quality of life in people ages 18 to 39, which the National Cancer Institute defines as “young adults.”

Their study, published in JAMA Network Open, found young adults who participated in the Bright IDEAS program showed significant reductions in depression and anxiety symptoms and improvements in their quality of life compared with members of the control group.

“Bright IDEAS participants felt less overwhelmed and more empowered,” said Katie Devine, Associate Director of the New Jersey Pediatric Hematology and Oncology Research Center of Excellence at Rutgers Cancer Institute, New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center together with RWJBarnabas Health. “This shows that a relatively brief intervention delivered by trained professionals can have a profound impact on patient well-being.”

Bright IDEAS teaches a five-step tactical approach to problem solving (IDEAS is an acronym standing for the steps of problem-solving: Identify the problem, Define your options, Evaluate options, Act and See if it worked) in a positive context (as in “bright”).

“The goal is by improving problem-solving skills, young adults will be better equipped to identify and act on problems and thus reduce symptoms of distress and improve quality of life,” said Devine, an author of the study who also is an associate professor at Rutgers Robert Wood Johnson Medical School.

The Bright IDEAS intervention is completed over six video sessions by licensed mental health professionals or supervised trainees who are trained to deliver the Bright IDEAS program.

“In each session, they address challenges and walk through the problems to identify solutions,” Devine says. “Instead of feeling overwhelmed about how to manage what is happening to them, they become empowered to manage their stressors.”

The study included 344 young adults between 18 and 39 who were within four months of a first cancer diagnosis and who were undergoing systemic therapy such as chemotherapy, radiation, immunotherapy or stem cell transplant at Rutgers Cancer Institute in New Brunswick, N.J., Memorial Sloan Kettering Cancer Center in New York, and Moffitt Cancer Center in Tampa.

Researchers conducted a randomized controlled trial, with half the participants receiving Bright IDEAS and the other half receiving usual psychosocial care of visits with a social worker and provided resources. The participants were surveyed to measure their symptoms at three and six months after enrollment.

“We are next planning a trial in community oncology settings, where most young adults receive their treatment, to make Bright IDEAS more accessible to patients who may not have access to large urban cancer centers,” Devine said.

Other Rutgers authors involved in the study are Sharon Manne, Kristine Levonyan-Radloff, Shengguo Li and Pamela Ohman Strickland.

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The findings were published on Feb. 23, 2026 in CANCER, a journal of the American Cancer Society.

“Over the past several years, we’ve had an increasing appreciation for the important relationship between cancer, its treatment, and mental health,” said lead author Julian Hong, MD, MS, of the University of California, San Francisco. “This study reproduces our prior work by leveraging the shared experience across the University of California system, reinforcing a relationship between mental health conditions and mortality for patients with cancer and highlighting the need to prioritize and manage mental health.”

The researchers used The University of California Data Discovery Platform, in which data on all patients at University of California–affiliated hospitals are recorded.

They identified adult patients with a cancer diagnosis and no documented mental health disorder prior to cancer diagnosis between 2013 and 2023.

Among 371,189 patients, 39,687 (10.6%) developed a mental health disorder within the first year after cancer diagnosis.

After adjusting the data for factors which might affect the primary outcome, the researchers reported that a mental health disorder diagnosis was linked to a 51% higher risk of all-cause death in the initial 1–3 years after cancer diagnosis. This elevated risk decreased to a 17% higher risk after 3–5 years. Then it disappeared.

The authors concluded, “Patients with cancer who experience a mental health condition are at an increased risk of all-cause mortality. This reinforces and emphasizes existing recommendations for prompt screening and management of distress and mental health following a cancer diagnosis.

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HPV is linked to six different kinds of cancer, including cervical, throat, anal, penile, vaginal and vulvar, and almost 40,000 new cancer cases each year in the U.S. Fortunately, a safe and effective vaccine is available for those between the ages of 9 and 45 to help to prevent these cancers.

“This is one of the few opportunities where we can prevent cancer with a vaccine,” said Hollings Cancer Center researcher Marvella Ford, Ph.D., associate director of Population Science and Community Outreach and Engagement.

In 2016, South Carolina ranked last in the U.S. in HPV vaccination rates. This alarming statistic led to an initiative by pediatricians from across the state and MUSC Hollings Cancer Center to increase access to and uptake of the vaccine.

“The fact that South Carolina was the last in the country for HPV vaccination prompted a lot of effort among South Carolina pediatric practices to improve the HPV vaccination rate,” said MUSC Children’s Health pediatrician James Roberts, M.D.

To complement those efforts, Ford and Roberts teamed up to launch the MUSC Hollings community health van in October of 2021 with funding from Healthy Me-Healthy South Carolina and the South Carolina Clinical and Translational Research Institute. Ford and Roberts had noted that some of the lowest rates of vaccination were seen in the state’s underserved and rural communities. The community health van travels to these communities, providing access to the HPV vaccine and other childhood vaccines. The MUSC team reports encouraging data from the first year of the program in a recent article in the Journal of Clinical Medicine.

Although the vaccine can be given between the ages of 9 and 45, the community health van focuses on vaccinating children between the ages of 9 and 18 because the vaccine is more effective when given at an earlier age, and medically underserved children in this age group are covered by the Center for Disease Control and Prevention’s Vaccines for Children Program. Both girls and boys are vaccinated.

“People sometimes think this vaccine is only for girls and women, but it is important for everyone to receive the vaccine,” said Ford.

Roberts points out that the vaccine is extremely safe because it contains no actual virus, only virus-like particles, meaning there is no chance of infection from the vaccine. These virus-like particles trigger the body’s defense, or immune system, and readies it to fight against future HPV infection.

In its first year, the community health van reached children in 21 of South Carolina’s 46 counties. The initiative began at a town hall meeting in Cherokee County, which had the lowest HPV vaccination rate in the state. Local community members gave testimonials about the importance of HPV vaccination, and the MUSC team answered questions. A video of this townhall event was made available to many other school districts across the state and has been watched more than 6,000 times.

Building on these early successes, Ford and Roberts hope to continue to expand the initiative to other counties in the state by partnering with school districts and community champions. The initiative includes educational sessions with parents of children eligible to receive the vaccine. During these sessions, researchers will evaluate parents’ perceptions, attitudes and beliefs about the HPV vaccine as well as their intentions to get their children vaccinated.

The community health van team also hopes to build on existing partnerships, such as that of MUSC and South Carolina State University, a historically Black university. The institutions jointly run the South Carolina Cancer Disparities Research Center (SC CADRE), which aims to build cancer health equity through research. SC CADRE provides selected SCSU students, known as scholars, the opportunity to join research teams at MUSC during the summer. One of those scholars, I’Ayana Sanders, is a co-author of the article and will help to enter and analyze data from the pre- and post-HPV educational sessions with parents to analyze the efficacy of the intervention.

Thanks to the combined efforts of pediatricians across the state and MUSC initiatives like the community health van, HPV vaccination rates in South Carolina are now on par with those of other states.

IMAGE: PICTURED FROM LEFT TO RIGHT:: MEDICAL UNIVERSITY OF SOUTH CAROLINA HOLLINGS CANCER CENTER COMMUNITY HEALTH VAN TEAM MEMBERS MINA PLATT, DR. MARVELLA FORD, MELANIE SLAN AND JOAN MCLAUREN. view more 

CREDIT: MEDICAL UNIVERSITY OF SOUTH CAROLINA

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Despite the commitment of medicines regulators to shared decision making and person centred care, the researchers say better information on the benefits and potential harms of medicines are needed to help inform treatment decisions, especially for patients with time limiting conditions such as advanced cancer.

To receive and participate in medical care, patients need high quality information about treatments, tests, and services, including information about the benefits of and risks from prescription drugs. Previous studies have looked at how information on drug risks and adverse effects is communicated to patients, but research on communication of drug benefits is limited.

To address this, researchers set out to assess the extent to which information about cancer drug benefits, and related uncertainties, is communicated to patients and doctors in regulated prescription drug information sources in Europe.

They reviewed official written and electronic information for clinicians (through a summary of product characteristics), patients (information leaflets) and the public (public summaries) for 29 new cancer drugs approved by the European Medicines Agency (EMA) during 2017-2019.

They then compared the information on drug benefits reported in these sources with the information available in regulatory assessment documents (known as European public assessment reports  or EPARs), which contain everything required for drug approval.

They found that both patient and public facing information sources were often lacking in relevance. For example, information on drug benefits was not reported in any patient leaflets, while other – potentially less relevant information for patients (eg. how a drug works in the body) – was consistently included.

They also found instances where the reporting of a study design and study findings was inconsistent with the information reported in EPARs and potentially misleading.

Important gaps and uncertainties in the evidence base were also rarely reported, particularly those that might be relevant and useful for patients, such as whether a drug extended survival or improved quality of life.

Finally, scientific concerns about the reliability of evidence on drug benefits, which were raised by European regulatory assessors for almost all drugs in the study sample, were rarely communicated to clinicians, patients, or the public.

The researchers acknowledge that their review may not have captured all information about each trial or drug benefits and uncertainties that might be relevant and useful for patients. What’s more, they included only new cancer drugs and it’s not clear whether these findings extend to other disease areas.

Nevertheless, this was a comprehensive review of documents which they say “identified important shortcomings in the communication of information on drug benefits and related uncertainties in regulated sources.”

The findings “highlight the need to improve the communication of the benefits and related uncertainties of anticancer drugs in regulated information sources in Europe to support evidence informed decision making by patients and their clinicians,” they conclude.

The takeaway message from this study is that information about drugs is rarely communicated well—and particularly not communicated well to patients, say BMJ editors in a linked editorial.

It also raises questions about whether this knowledge gap is interfering with shared decision making and whether new ways to present information such as visual representation of data on benefits and harms – used for covid-19 vaccines – could be applied to other types of medicines.

“The trust between patients and healthcare providers remains pivotal in ensuring that patients are fully informed about benefits and harms of drugs,” they write. “But regulatory agencies should pay closer attention to important gaps in information for patients, and further research should aim to determine more precisely where these gaps occur and to work with patients to fill them.”

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“There is no standard of care for treating cancer pain and managing opioids in people who come into their cancer diagnosis with a history of substance use, or who are at increased risk for adverse events due to prescription opioid misuse behaviors, such as taking more opioids than prescribed,” said first author Katie Fitzgerald Jones, M.S.N., a palliative and addiction nurse practitioner at VA Boston Healthcare System and Ph.D. candidate at Boston College. “As a first step towards improving care of these patients, our study surveyed clinicians to understand how they treat patients with opioid complexity.”

The study was led by Jones and study principal investigator and senior author Jessica Merlin, M.D., Ph.D., associate professor of general internal medicine at the University of Pittsburgh School of Medicine and co-director of the Palliative Recovery Engagement Program at UPMC, a clinic that serves patients with serious illnesses, like cancer, who also struggle with opioid use disorder or prescription opioid misuse. In collaboration with colleagues at RAND, the investigators used an online Delphi study platform to explore consensus among 120 palliative care and addiction experts about how they would approach treatment of a hypothetical 50-year-old patient with advanced cancer who has cancer-related pain and either a history of opioid use disorder or prescription opioid misuse.

Participants were asked to rate and comment on various management strategies, such as prescribing methadone and buprenorphine. Experts indicated that both of these medications are an appropriate approach to treating cancer pain in a patient with a history of an opioid use disorder.

Prescribing methadone and buprenorphine for pain requires clinicians to hold only a Drug Enforcement Administration (DEA) license, but there are additional barriers to prescribing the very same drugs for opioid use disorder. Methadone can be legally used to treat opioid use disorder only in licensed methadone treatment programs. Additionally, clinicians must have what’s known as a DEA X-waiver to prescribe buprenorphine for opioid use disorder. According to Jones and Merlin, only a small fraction of oncologists and palliative care clinicians hold an X-waiver, a hurdle for cancer patients who could benefit from this medication.

“Because of the way that methadone and buprenorphine are regulated — one way for pain, another way for addiction — addiction treatment is isolated from mainstream medical care, including cancer care,” said Merlin. “It’s othering, and it adds to the stigma of opioid use disorder.”

Study participants agreed that it is inappropriate to refer a patient with advanced cancer to a methadone treatment program because of the burden of frequent, sometimes daily, visits alongside cancer treatments.

“Interestingly, experts in the study suggested that it was appropriate to prescribe methadone outside of the context of a licensed methadone treatment program for pain in cancer patients with a history of opioid use disorder — even though this is murky legal territory,” said Merlin. “This finding highlights the need to improve access to this drug.”

According to Jones, methadone is dosed differently for pain and opioid use disorder, and more research is needed to understand the best approach for treating cancer pain and opioid use disorder concurrently.

In scenarios where the hypothetical cancer patient did not have a history of opioid use disorder but was misusing opioids — taking higher doses than prescribed or taking a benzodiazepine that wasn’t prescribed — experts recommended continuing their opioid regime but increasing monitoring through more visits or shorter prescriptions. According to Merlin, this was an interesting finding because these scenarios pose increased risk for overdose and opioid-related harms. Despite these risks, experts were reluctant to transition to buprenorphine, a safer opioid with less overdose potential.

“Drawing from our other research, we think there are many reasons that clinicians were hesitant to use buprenorphine, including knowledge gaps, lack of guidelines for management of opioid misuse, regulation of buprenorphine and stigma,” said Jones.

The researchers say that better education around buprenorphine and cancer pain management in the context of an opioid use disorder or opioid misuse is needed.

“There is a tendency to ignore treatment of opioid use disorder in advanced cancer patients because people think, ‘Oh, this person has bigger fish to fry,’ but that’s not a very patient-centric way of looking at things,” said Merlin. “We know that opioid use disorder is a really important factor in quality of life, so addressing opioid addiction and prescription opioid misuse in people with advanced cancer is really critical.”

Merlin and Jones are working to educate palliative care clinicians around the country about using buprenorphine to treat opioid use disorder, including encouraging them to get X-waivers to treat addiction alongside pain.

“If we are going to prescribe opioids for pain, it is our moral obligation to also treat an important consequence of that opioid prescribing — opioid addiction — if and when it occurs in our patients,” said Jones.

Other authors on the study include Dmitry Khodyakov, Ph.D., and Emily Dao, M.S., of the RAND Corporation; Robert Arnold, M.D., Hailey Bulls, Ph.D., and Jane Liebschutz, M.D., M.P.H., all of Pitt; Jennifer Kapo, M.D., M.S.C.E., of the Yale University School of Medicine; Diane Meier, M.D., of the Icahn School of Medicine at Mount Sinai; Judith Paice, Ph.D., R.N., of Northwestern University; and Christine Ritchie, M.D., M.S.P.H., of Massachusetts General Hospital.

This research was supported by Cambia Health Foundation and the National Institute of Nursing Research (F31NR019929-01).

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According to the World Health Organisation, in 2020 the global cancer burden was estimated at 19.3 million new cases and 10 million deaths. WHO experts believe that an estimated 30% of new cases could be prevented, and about the same proportion could be cured, with early detection.

Today, a ‘lab-on-a-chip’ is a miniature sensor device capable of performing complex biochemical analysis which are considered one of the most promising approaches to early cancer detection. Russian researchers have developed a new hybrid nanophotonic-microfluidic sensor for highly sensitive analysis of liquids and gases at very low concentration in solutions.

Gregory Goltsman, HSE MIEM Professor

“Our study is an important step towards creating a compact lab-on-a-chip device capable of not only performing a whole set of blood tests but detecting cancer biomarkers at an early stage using a very small amount of the patient’s blood. Ideally, we aim to create a small portable device neded just a drop of blood. By pressing a button, the doctor would see the results, e.g., that the parameters are normal or that further tests are required.”

The current device consists of nanophotonic optical sensors on a chip in combination with microfluidic channels above the sensor surface. Fluids or gases pumped through the channels affect the propagation of optical radiation in the highly sensitive nanophotonic devices, changing the output’s spectral characteristics. By examining these changes, researchers can determine the sample’s composition.

A special feature of the device is the tiny size of the microfluidic channels that deliver specimens to the sensors. This makes it possible to obtain results even from very small samples, something that can be critical when on-site analysis is not feasible and specimens must be transported elsewhere for examination.

Human blood contains certain components which can be valuable for preliminary diagnoses of oncology diseases. Such components include extracellular vesicles (exosomes). Exosomes are microscopic vesicles released into the intercellular space by tissue and organ cells.

“Cells communicate among themselves by using extracellular vesicles, such as exosomes, to send out messages”, says Dmitry Gorin, professor at the Skolkovo Institute of Science and Technology. However, certain factors—either internal (genetic predisposition) or external (environmental, such as radiation) —can disrupt a cell’s normal functioning, causing it to send the wrong messages, leading to uncontrolled cell division and tumour growth”.

At an early stage of cancer, exosome blood concentrations tend to increase to reach analytically significant values, signalling the presence of cancer, so this makes exosomes a potentially useful biomarker in oncology. The research team plan to further refine their device so that it may be used for this method of cancer detection.

So far, the sensor has been tested not on blood samples but on water solutions of isopropyl alcohol in 20 different concentrations, from 0.08% to 72% by weight. Since alcohol is highly soluble in water, it was possible to use very low concentrations. For example, the sensor detected isopropanol in a solution containing 12 molecules of alcohol per one million molecules of water. Currently, the device can analyse only two-component solutions, but the authors plan to make it suitable for multi-component analytes by covering special receptors (aptamers, antibodies, DARPins, and peptides) onto the sensor surface using microfluidic channels.

“Today, the experimental equipment needed for the device operation is rather bulky. The setup includes a peristaltic pump, a tuneable laser, a photodetector, a chip, and a PC for processing the data”, explains the paper’s author Aleksei Kuzin, HSE graduate and current doctoral student at Skoltech. ‘In the future, we hope to produce a compact and portable device for rapid testing that will reduce the time and cost of cancer diagnosis, monitoring and treatment response assessment”.

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“What we see is that, among patients with type 2 diabetes, many cancer cases are preventable. These results are an important contribution that enhances our understanding of the connection between glucose control and cancer prevention,” said lead author Kajsa Sjöholm, Associate Professor of Molecular Medicine at Sahlgrenska Academy, University of Gothenburg in Sweden.

As background the authors noted that there have been few studies on the association between weight loss, risk of cancer and glucose control in patients with both obesity and type 2 diabetes.

“Although bariatric surgery has been shown to reduce cancer risk in patients with obesity,” they wrote, “the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study.”

The investigators evaluated data on 701 subjects who had been diagnosed with obesity and type 2 diabetes at the SOS study baseline. Subsequently, 393 had undergone bariatric surgery and 308 had received conventional obesity treatment.

Median follow-up time was 21.3 years.

The researchers obtained Information on cancer events from the Swedish National Cancer Register.

They reported that the incidence rate for first-time cancer was 9.1 per 1,000 person-years in subjects diagnosed with obesity and diabetes who were treated with bariatric surgery, and 14.1 per 1,000 person-years in subjects treated with usual obesity care, a significant difference (P = 0.008).

Diabetes remission at the 10-year follow-up was also associated with a significant reduced cancer incidence (P = 0.003).

The authors concluded, “These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk.”

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Standard-issue CAR T cells are designed in the laboratory to recognise specific markers on cancer cells. When these CAR T cells are given back to a patient, they proliferate and go on the attack, acting as a kind of ‘living drug’.

Despite their usefulness for treating blood cancers, there are several limitations of current CAR T models. One is that the CAR T cells can only kill cancer cells that contain the marker they are designed to recognise. But it is not uncommon for cancer cells to stop making this marker and thus to ‘escape’ from the therapy.

A second problem is that CAR T cells can become ‘exhausted’ — and even inhibited by the cancer cells themselves. Lastly, existing CAR T cells work well only against blood cancers that the CAR T cells can easily reach. Against dense solid tumours in the lung or breast, they are mostly powerless.

To overcome these hurdles, the team of SKI researchers explored a novel approach to developing CAR T cells that can generate a small-molecule, anti-cancer drug locally at the disease site. This system can deliver a toxic drug payload directly to a tumour, killing both tumour cells that contain the cancer marker as well as those cancer cells nearby that do not. What’s more, the engineered cells can produce the drug even after they become exhausted, and the drug is not suppressed by the cancer.

“We call them SEAKER cells,” says physician-scientist David A. Scheinberg, Chair of the Molecular Pharmacology Program in SKI who also directs the Center for Experimental Therapeutics. “SEAKER stands for Synthetic Enzyme-Armed KillER cells. These cells combine the target-seeking power of immune cells with the ability to locally generate a potent anticancer drug for double effect.”

The cancer-fighting molecule is one that SKI Chemical Biology Program Chair Derek Tan — Dr. Scheinberg’s collaborator on the project — discovered previously while developing antibiotics. The molecule, called AMS (5′-O-sulfamoyl adenosine), is so powerful that it cannot be injected directly into an animal’s bloodstream. But when it is produced locally just at the site of a tumour, it is effective at safely killing cancer cells in mice. The scientists have not yet tested the technology in people.

Details about the SEAKER platform, which the scientists say has applicability to both cancer and other diseases, were published on December 30, 2021, in Nature Chemical Biology.

The SEAKER approach

The idea of using CAR T cells to deliver additional therapeutic agents is not new. Several research groups have shown it’s possible to get them to make immune proteins like antibodies and cytokines. However, getting CAR T cells to produce a small-molecule cancer drug is a trickier prospect.

The SEAKER system links an anti-cancer molecule to another chemical, in this case either glutamate or cephalosporin, that ‘masks’ its function. The genetically engineered CAR T cells are designed to make an enzyme that cuts the masking molecule from the drug. The enzyme acts as scissors, activating the drug at the site of the tumour.

It’s very exciting that we got it to work.

The scientists tested their SEAKER cells on both cancer cells growing in a dish and in mouse models. In both cases, the SEAKER cells performed better than regular CAR T cells at killing the cancer cells. The SKI team also showed that their SEAKER cells work with several different prodrugs and several different cleaving enzymes

Now that SEAKER cells have been shown to work in mice, there has been a lot of interest in the approach and a company called CoImmune has already licensed the technology from MSK to develop the CAR T cell technology for human trials.

Dr. Scheinberg speculates that a clinical trial in cancer is about two to three years away.

Key Takeaways

• Chimeric antigen receptor (CAR) T cell therapy is a type of immunotherapy that uses genetically modified versions of a person’s own immune cells to fight cancer.
• Current models of CAR T cells have several limitations, including a tendency to stop working after a period of time.
• A team of scientists at MSK’s Sloan Kettering Institute have developed new versions of CAR T cells that overcome some of these limitations.
• These new CAR T cells act as ‘micropharmacies’, delivering small-molecule anticancer drugs directly to the site of a tumour.

Reference

Gardner, T.J., Lee, J.P., Bourne, C.M. et al. Engineering CAR-T cells to activate small-molecule drugs in situ. Nat Chem Biol (2021). https://doi.org/10.1038/s41589-021-00932-1

Image

SKI scientists David Scheinberg and Derek Tan

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Cancer deaths rose to 10 million and new cases jumped to over 23 million globally in 2019, according to a new scientific study from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine.

At the start of the decade in 2010, total cancer deaths numbered 8.29 million worldwide and new cancer cases were at 18.7 million; the counts by the end of the decade in 2019 represent increases of 20.9% and 26.3%, respectively.

The paper was published on December 30, 2021 in JAMA Oncology, and is part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019).

The researchers estimated cancer burden and trends globally for 204 countries and territories. They found that cancer was second behind only cardiovascular diseases in the number of deaths, disability-adjusted life years (DALYs), and years of life lost (YLLs) among 22 groups of diseases and injuries globally in 2019. Within the total cancer burden, the five leading causes of cancer-related DALYs for both sexes combined were tracheal, bronchus, and lung (TBL) cancer; colon and rectum cancer; stomach cancer; breast cancer; and liver cancer. TBL cancer was the leading cause of cancer deaths in 119 countries and territories for males and 27 countries and territories for females.

Although the absolute burden of cancer increased in both deaths and new cases from 2010 to 2019, the global age-standardized mortality and incidence rates decreased by 5.9% and 1.1%, respectively. From a country perspective, the age-standardized mortality rate decreased in 131 countries and territories and the age-standardized incidence rate lessened in 75 countries and territories. The small percentage declines globally are promising, but the researchers caution that there may be setbacks in cancer care and outcomes due to COVID-19. The effects of the pandemic on cancer morbidity, mortality, and prevention and control efforts were not accounted for in this GBD study, which analyzed global cancer burden through 2019.

The authors also analyzed cancer burden based on Socio-demographic Index (SDI), a composite measure of income per capita, average years of education, and total fertility rate for people younger than 25 years of age.

While the global trend for age-standardized mortality and incidence rates is encouraging, the reduction in rates appears to be driven by higher SDI locations. For mortality, age-standardized rates decreased in the middle, middle-high, and high quintiles and increased in the low and low-middle quintiles. Similarly, for incidence, the age-standardized rates decreased in the high-middle and high quintiles — with the largest decrease in the high SDI quintile — while increasing in the low, low-middle, and middle SDI quintiles.

“Ensuring that global progress against cancer burden is equitable is crucial,” said Dr. Jonathan Kocarnik, lead author on the study and Research Scientist at IHME. “This will require efforts to reduce disparities in cancer prevention, treatment, and survival, and the incorporation of local needs and knowledge into tailored national cancer control plans.”

Dr. Kocarnik and his co-authors suggested that the larger increases in the lower SDI quintiles likely reflect ongoing epidemiological transitions, demographic shifts, and disparities in cancer prevention, care, and control. Even without accounting for the COVID-19 pandemic, the absolute burden of cancer is already growing substantially worldwide.

Some additional findings from the study:

• Breast cancer was the leading cause of cancer-related deaths among females worldwide, including for 119 countries.
• On a global scale, 96.9% of cancer-related DALYs, which is the sum of YLLs and years lived with disability, can be attributed to YLLs or premature death.
• Of the 22 groups of diseases and injuries in the GBD study, total cancer is the leading cause of DALYs for the high SDI quintile and among the top five causes of DALYs for three of the remaining four SDI quintiles.

Journal Reference:

1. Jonathan M. Kocarnik et al. Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019. JAMA Oncology, 2021; DOI: 10.1001/jamaoncol.2021.6987

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The discovery, reported in Nature Cell Biology, is a significant advance in understanding the role extracellular vesicles and nanoparticles play in shuttling important chemical “messages” between cells, both in health and disease.

“We’ve identified a number of biomarkers and therapeutic targets in cancer and potentially in a number of other disease states that are cargo in these supermeres,” said the paper’s senior author, Robert Coffey, MD. “What is left to do now is to figure out how these things get released.”

Coffey, the Ingram Professor of Cancer Research and professor of Medicine and Cell & Developmental Biology, is internationally known for his studies of colorectal cancer. His team is currently exploring whether the detection and targeting of cancer-specific nanoparticles in the bloodstream could lead to earlier diagnoses and more effective treatment.

In 2019 Dennis Jeppesen, PhD, a former research fellow in Coffey’s lab who is now a research instructor in Medicine, used advanced techniques to isolate and analyze small membrane-enclosed extracellular vesicles called “exosomes.”

That year, using high-speed ultracentrifugation, another of Coffey’s colleagues, Qin Zhang, PhD, research assistant professor of Medicine, devised a simple method to isolate a nanoparticle called an “exomere” that lacks a surface coat.

In the current study, Zhang took the “supernatant,” or fluid that remains after the exomeres have been spun into a “pellet,” and spun the fluid faster and longer.

The result was a pellet of nanoparticles isolated from the supernatant of the exomere spin — which the researchers named supermeres. “They’re also super-interesting,” Coffey quipped, “because they contain many cargo previously thought to be in exosomes.”

For one thing, supermeres carry most of the extracellular RNA released by cells and which is found in the bloodstream. Among other functional properties, cancer-derived supermeres can “transfer” drug resistance to tumor cells, perhaps via the RNA cargo they deliver, the researchers reported.

Supermeres are important carriers of TGFBI, a protein that in established tumors promotes tumor progression. TGFBI thus may be a useful marker in liquid biopsies for patients with colorectal cancer, the researchers noted.

They also carry ACE2, a cell-surface receptor that plays a role in cardiovascular disease and is the target of the COVID-19 virus. This raises the possibility that ACE2 carried by supermeres could serve as a “decoy” to bind the virus and prevent infection.

Another potentially important cargo is APP, the amyloid-beta precursor protein implicated in the development of Alzheimer’s disease. Supermeres can cross the blood-brain barrier, suggesting that their analysis could improve early diagnosis or possibly even targeted treatment of the disease.

“The identification of this rich plethora of bioactive molecules … raises interesting questions about the function of supermeres, and heightens interest in the potential of these particles as biomarkers for diseases,” researchers at the University of Notre Dame noted in a review published with the paper.

Zhang, Jeppesen and James Higginbotham, PhD, research instructor in Medicine, are the paper’s first authors.

Other VUMC co-authors: Ramona Graves-Deal, Vincent Q. Trinh, MD, Marisol Ramirez, MS, Yoojin Sohn, Abigail Neininger, Nilay Taneja, PhD, Eliot McKinley, PhD, Hiroaki Niitsu, MD, PhD, Zheng Cao, MD, PhD, Rachel Evans, Sarah E. Glass, Kevin Ray, William Fissell, MD, Salisha Hill, MS, Kristie Rose, PhD, Mary Kay Washington, MD, PhD, Gregory Ayers, MS, Dylan Burnette, PhD, Jeffrey Franklin, PhD, Youngmin Lee, MD, PhD, and Qi Liu, PhD.

Research support included National Institutes of Health grants GM125028, CA218386, CA211015, CA197570, CA236733, CA241685 and CA229123, the Nicholas Tierney GI Cancer Memorial Fund, and an American Heart Association Postdoctoral Fellowship.

Journal References:

1. Qin Zhang, Dennis K. Jeppesen, James N. Higginbotham, Ramona Graves-Deal, Vincent Q. Trinh, Marisol A. Ramirez, Yoojin Sohn, Abigail C. Neininger, Nilay Taneja, Eliot T. McKinley, Hiroaki Niitsu, Zheng Cao, Rachel Evans, Sarah E. Glass, Kevin C. Ray, William H. Fissell, Salisha Hill, Kristie Lindsey Rose, Won Jae Huh, Mary Kay Washington, Gregory Daniel Ayers, Dylan T. Burnette, Shivani Sharma, Leonard H. Rome, Jeffrey L. Franklin, Youngmin A. Lee, Qi Liu, Robert J. Coffey. Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets. Nature Cell Biology, 2021; DOI: 1038/s41556-021-00805-8
2. James W. Clancy, Alex C. Boomgarden, Crislyn D’Souza-Schorey. Profiling and promise of supermeres. Nature Cell Biology, 2021; DOI: 1038/s41556-021-00808-5

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