Tag: Medication

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Elraglusib Delivers Rare Survival Benefit in Pancreatic Cancer

A randomized Phase II trial offers a rare signal of progress in pancreatic cancer, a disease long marked by therapeutic stagnation, with investigators reporting that the experimental agent elraglusib (9-ING-41) improved survival when added to standard chemotherapy of gemcitabine plus nab-paclitaxel (GnP).

Published in Nature Medicine, the study evaluated the novel drug—developed within an academic setting at Northwestern University—in patients with metastatic pancreatic cancer. The findings suggest that targeting glycogen synthase kinase-3 beta (GSK-3β), a protein not previously exploited clinically in this disease, could open a new therapeutic avenue.

“This is one of the first trials in a randomized setting that has been positive in pancreatic cancer in the last decade,” said Devalingam Mahalingam, MD, PhD, a study leader at Northwestern University. “There was really a barren spell… many failed trials. So it’s nice to see a positive trial.”

A modest but meaningful survival gain

The multicenter trial enrolled 233 patients across North America and Europe, randomly assigning them to receive chemotherapy alone or in combination with elraglusib. Patients receiving the combination lived a median of 10.1 months compared with 7.2 months for chemotherapy alone, and the addition of elraglusib reduced the risk of death by 38%.

Perhaps more striking, survival at one year doubled in the experimental arm (44% vs. 22%), and approximately 13% of patients remained alive at two years—an uncommon outcome in metastatic pancreatic cancer.

Mahalingam emphasized that the benefit was not necessarily reflected in higher tumor response rates. Instead, patients appeared to derive prolonged disease control.

“We didn’t really see much more tumor shrinkage compared to chemo alone,” he said. “But patients stayed on the treatment arm longer… sometimes they would reduce or drop the chemo and just stay on the drug.”

This pattern, he added, points toward a mechanism beyond direct cytotoxicity.

A different mechanism of action

Unlike conventional chemotherapy, which primarily targets rapidly dividing cells, elraglusib appears to act on the tumor microenvironment—the complex ecosystem of immune cells, stromal tissue, and signaling molecules surrounding cancer cells.

The drug inhibits GSK-3β, a protein involved in multiple cellular processes, including metabolism, signaling pathways, and immune regulation. While broadly expressed in normal tissues, GSK-3β can be co-opted by tumors to promote growth and suppress immune responses.

“GSK-3 beta is expressed in many tumors,” Mahalingam said. “It’s part of a central regulator of normal cell functioning… but in cancer, this pathway is used to allow for tumor growth and proliferation.”

Preliminary analyses from the trial suggest that elraglusib may enhance antitumor immunity. Biopsies and blood-based markers indicated changes consistent with immune activation, supporting the hypothesis that the drug helps re-engage the immune system in a tumor type typically resistant to immunotherapy.

“We saw what we call immunomodulatory effects,” Mahalingam noted. “The immune cells might be driving some of the survival benefit we see.”

This is particularly notable given the long-standing failure of checkpoint inhibitors in pancreatic cancer, a tumor characterized by a highly immunosuppressive microenvironment.

Developed in academia

Elraglusib’s development trajectory also sets it apart. The compound originated in academic laboratories more than a decade ago, with early work spanning Northwestern University, the University of Illinois Chicago, and the Mayo Clinic.

“This is what not many drugs are—developed within an academic setting,” Mahalingam said. “It was founded in a chemistry lab… and then moved into a spin-off company to raise funding for trials.”

After preclinical development between 2010 and 2015, the drug entered early-phase trials around 2017 and has since been evaluated across multiple tumor types, with a recent focus on pancreatic cancer.

The randomized Phase II trial marks the first time a GSK-3β inhibitor has demonstrated efficacy beyond early-stage testing.

Broad eligibility, real-world relevance

Investigators designed the study with relatively broad inclusion criteria, enrolling patients with high tumor burden and poor nutritional status—characteristics common in real-world pancreatic cancer populations but often excluded from clinical trials.

“We allowed patients with very large volumes of disease,” Mahalingam said. “We did not restrict patients for albumin… we didn’t engineer the study to look better.”

This approach may partly explain the modest median survival difference, as some patients progressed too quickly to benefit. However, it also strengthens the generalizability of the findings.

Safety and next steps

Side effects associated with elraglusib were generally manageable and consistent with chemotherapy, including hematologic toxicities, fatigue, and reversible vision changes.

The next step will be a confirmatory Phase III trial, with discussions ongoing with regulators.

“We really need to confirm the studies in a large phase three trial,” Mahalingam said, adding that trial design considerations include how to integrate emerging therapies such as KRAS inhibitors.

Investigators are also exploring combination strategies, including pairing elraglusib with immunotherapy or alternative chemotherapy regimens. Early safety studies suggest such combinations are feasible, though efficacy data remain limited.

Potential beyond pancreatic cancer

Given the central role of GSK-3β in multiple cellular pathways, researchers are already investigating the drug’s potential in other malignancies, including hematologic cancers and pediatric tumors such as Ewing sarcoma and medulloblastoma.

“This is a new class of potential cancer therapeutics,” Mahalingam said. “Certainly, there would be excitement in seeing where this target can be applied to other tumors.”

While challenges remain, the trial’s results offer cautious optimism in a field where progress has been incremental at best.

“Even if it means that this class of drugs can be used for future drug development,” Mahalingam said, “it gives an opportunity to expand therapeutic potential—not just for pancreatic cancer, but beyond.”

The post Elraglusib Delivers Rare Survival Benefit in Pancreatic Cancer appeared first on Inside Precision Medicine.

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Public Perceptions of AI in Medicine and Implications for Future Medical Education: Cross-Sectional Survey

Background: The integration of artificial intelligence (AI) into clinical practice is contingent on public trust. This trust often depends on physician oversight, yet a significant gap exists between the need for AI-competent physicians and the current state of medical education. While the perspectives of students and experts on this gap are known, the views of the US general public remain largely unquantified. Objective: This study aimed to assess US public perceptions regarding AI in medicine and the corresponding emergent needs for medical education. We specifically sought to quantify public trust in different diagnostic scenarios, concerns about physician overreliance on AI, support for mandatory AI education, and priorities for the future focus of medical training. Methods: We conducted a cross-sectional, web-based survey of adults in the United States in November 2025. Participants (N=524) were recruited via SurveyMonkey Audience. We calculated descriptive statistics, frequencies, proportions (percentages), and 95% CIs for all main survey items. Results: A total of 524 participants completed the survey. Most (n=329, 62.8%; 95% CI 58.6%‐66.9%) placed the most trust in a physician’s diagnosis based on their expertise alone; only 7.8% (n=41; 95% CI 5.5%‐10.1%) trusted an AI-first diagnostic model. Trust was highly contingent on training: 93.9% (n=492) of participants rated formal physician training on AI limitations as “essential” or “very important.” Widespread concern about physician overreliance on AI was reported, with 81.1% (n=425) being “very concerned” or “extremely concerned.” Consequently, 85.1% (n=446) agreed or strongly agreed that training on AI use, ethics, and limitations should be mandatory in medical school. When asked about future educational priorities, 70.2% (n=368; 95% CI 66.3%‐74.1%) believed that medical education should focus on human-centered skills (eg, empathy and communication) over clinical skills. Conclusions: The US public expressed conditional trust in medical AI, strongly preferring physician-led and critically supervised models. These findings reveal a clear public mandate for medical education reform. The public expects future physicians to be mandatorily trained to appraise AI, understand its limitations, and refocus their professional development on the human-centered skills that technology cannot replace.
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Earlier Surveillance Warranted for Young Cancer Survivors

Approximately one in six adolescents and young adults who survive cancer will be diagnosed with another cancer within 30 years of their initial diagnosis, making their cancer risk more than double that of the general population, shows data from Canada.

“When combined with the relatively high survival rates in this age range, at approximately 86%, there is a growing population of young cancer survivors that will be adversely affected by their cancer diagnosis and its treatment even decades later,” write Miranda Fidler-Benaoudia, a cancer epidemiologist at the University of Calgary Cumming School of Medicine and Cancer Care Alberta, and co-authors in the Canadian Medical Association Journal.

“Given that subsequent primary neoplasms are major contributors to morbidity and premature mortality, these findings underscore the need for innovative solutions to prevent, detect, and treat subsequent primary neoplasms among survivors of adolescent and young adult cancer,” they say.

Although global data suggest that adolescent and young adult cancer survivors are 1.6 to 4.3 times more likely to develop a subsequent cancer than expected in the general population, data are limited for Canada, where cancer rates among this group increased annually by 1.3% from 1998 to 2012, with an estimated 8739 adolescents and young adults diagnosed with cancer in 2022.

The Alberta Adolescent and Young Adult Cancer Survivor Study retrospectively reviewed data for 24,459 people with a neoplasm first diagnosed between 1983 and 2017 at age 15 to 39 years. Of these, 1442 (5.9%) had subsequent primary neoplasms, 1129 (7.6%) of which occurred among the 14,818 people who were five-year survivors.

The researchers report that, overall, adolescent and young adult cancer survivors were 2.2 times more likely to develop a subsequent primary neoplasm than would be expected in the general population, equating to 31.7 excess neoplasms per 10,000 person–years.

For five-year survivors, the incidence was twofold higher versus the general population with an excess risk of 35.7 per 10,000 person–years.

The greatest excess risks occurred among survivors of breast cancer (85.8 per 10,000 person–years), lymphomas other than Hodgkin lymphoma or non-Hodgkin lymphoma (82.0 per 10,000 person–years), and oral cavity, lip, and pharyngeal cancer (74.7 per 10,000 person–years).

Conversely, no significant excesses were observed for survivors of acute myeloid leukemia, central nervous system cancers, ovarian cancer, nonovarian and nontesticular gonadal and related tumors, stomach cancer, lung, bronchial, and tracheal cancer, and endometrial cancer.

After five-year survival, the 30-year cumulative incidence of a subsequent primary neoplasm was 17.7% overall, with incidence highest among survivors of cancers of the oral cavity, lip, or pharynx (28.9%), breast cancer (27.3%), colon cancer (23.5%), and Hodgkin lymphoma (22.7%).

Importantly, the team found that the absolute difference in cumulative incidence between the survivors and general population grew as time since diagnosis increased; for example, for five-year survivors of breast cancer, the absolute difference was 2.9% at 10 years postdiagnosis compared with 12.7% at 30 years postdiagnosis.

“Although people with nearly all types of adolescent and young adult cancer investigated were at an increased risk of developing a subsequent primary neoplasm, survivors of Hodgkin lymphoma and breast cancer were identified as particularly vulnerable populations, with nearly one-third of subsequent primary neoplasms occurring after five-year survival diagnosed in these survivor groups,” Fidler-Benaoudia et al remark. “These findings are consistent with previous studies and reflect the established late effects of radiotherapy, chemotherapy, and hormone therapy.”

However, they also note that genetic factors may play a role, and that genetic counseling and education on maintaining healthy lifestyles are important in caring for survivors.

The most common subsequent primary neoplasms were breast (27.1%), digestive (11.9%), hematopoietic (10.6%), or respiratory (6.8%) cancers, together accounting for nearly 60% of subsequent primary neoplasms.

Fidler-Benaoudia and colleagues say that their findings “offer valuable directions for research and cancer control.”

They point out that at present there are no risk-based survivorship care guidelines that cover the entire age range of the adolescent and young adult cancer population.

“Although both pediatric and adolescent and young adult cancer survivors are at increased risks for late effects, the magnitude of these risks varies and implications for care can differ; thus, clinical investigations that assess the association of treatment exposures with late effects like subsequent primary neoplasms should be a research priority,” the authors write.

They also stress that further work is needed to expand inclusion criteria for early high-risk screening initiatives and to develop specialized treatment guidelines that balance curing the subsequent primary neoplasm while effectively managing the survivors’ late effects.

The post Earlier Surveillance Warranted for Young Cancer Survivors appeared first on Inside Precision Medicine.

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Syncing Exercise to Body Clock Maximizes Cardiovascular Benefits

Timing exercise according to a person’s natural propensity towards being a “morning lark” or an “night owl” could maximize its cardiovascular benefits, a randomized trial suggests.

Matching exercise according to individual body clocks maximized the sleep quality and several parameters of cardiovascular health of middle-aged adults with preclinical risk factors.

The findings highlight the added value of incorporating circadian biology into exercise plans to optimize health outcomes.

Reporting their findings in Open Heart, the researchers suggest that assessing for chronotype—the predisposition towards morningness or eveningness—should be considered when prescribing exercise for those at risk of cardiometabolic disease.

“Our study shows that when you exercise may be just as important as how you exercise,” researcher Arsalan Tariq, PhD, from the University of Lahore, explained to Inside Precision Medicine.

“Aligning workouts with an individual’s biological clock significantly amplifies cardiovascular and metabolic benefits, offering a simple way to personalize prevention and improve adherence.”

A person’s chronotype affects their sleeping patterns, hormonal secretion, and energy levels during the day through an internal timing mechanism.

This is regulated by the circadian clock in a system that influences various physiological processes including blood pressure, heart rate, glucose metabolism, and vascular function.

Tariq and team examined how timing exercise affected key indicators of cardiovascular health among at-risk middle-aged adults.

Participants were aged 40 to 60 years and had at least one cardiovascular risk factor, such as high blood pressure, overweight, or obesity. The group also included those with a family history of premature cardiovascular disease.

Participants were randomly assigned to exercise at a time that either matched or did not match their chronotype, between 8am and 11am or between 6pm and 9pm.

This consisted of five, 40-minute sessions per week of supervised moderate intensity aerobic exercise such as brisk or treadmill walking for 12 weeks.

Of the 134 participants who completed the 60 sessions, 70 were larks—34 of whom had exercise matched with chronotype—and 64 were owls, with 30 matched to chronotype.

Measurements taken at the start of the trial and three days after it finished showed particular improvements in sleep and systolic blood pressure among those matched with chronotype.

Sleep quality improved by 3.4 points in matched participants versus 1.2 in the unmatched on the Pittsburgh Sleep quality Index. Systolic blood pressure dropped by 10.8 mmHg compared with 5.5mmHg in matched versus unmatched groups, respectively.

Chronotype-aligned exercise also led to significantly greater improvements in diastolic blood pressure, heart rate variability, peak oxygen consumption, low-density lipoprotein, and fasting glucose compared with misaligned exercise.

“Personalized, time-matched exercise interventions may become a practical strategy in clinical and public health settings, potentially leading to better outcomes and improved engagement,” the researchers reported.

“Future research and guidelines may consider circadian factors as a core component of lifestyle-based disease prevention.”

The post Syncing Exercise to Body Clock Maximizes Cardiovascular Benefits appeared first on Inside Precision Medicine.

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STAT+: A $15 AI test, Project Glasswing, and how Doctronic pilot blindsided Utah medical board

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<![CDATA[How clinicians choose TRD care: patient preferences, access barriers, and rapid glutamatergic options like esketamine for suicidal depression.]]>
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Rapid expansion of genotype D1.1 A(H5N1) influenza viruses in wild birds across North America during the 2024 migratory season

Nature Medicine, Published online: 15 April 2026; doi:10.1038/s41591-026-04300-1

Using active and passive genomic surveillance, researchers observed the rapid spread of high pathogenicity avian influenza H5N1 D1.1 viruses in wild birds during the 2024 migratory season, which coincided with detection in humans, but did not identify mammalian adaptive markers in viruses from wild birds.