Background: The original counterclockwise study carried out in the late 1970s provided an extreme example of “reminiscence therapy,” reporting improvements in older adults’ cognitive and physical functioning after they had lived for 5 days in a house set up as if decades earlier (the 1950s). We tested a virtual reality (VR) analog of this approach, enhanced by embodying participants in a virtual body that looked like themselves at the corresponding younger age. Objective: This study aimed to examine whether brief VR exposures combining (1) embodiment in a virtual body as one’s younger self and (2) immersion in an iconic past event improve age-related subjective and performance outcomes compared with a current-self VR control condition. Methods: We carried out a between-groups study with 23 healthy older adults (aged 65‐85 years; mean age 71.2, SD 4.03 years). Participants were randomly allocated to either a Young Self condition (n=11; mean 72.3, SD 4.17), where they were embodied in a virtual body that looked like themselves from the 1960s, or in a Current Self control condition (n=12; mean 70.1, SD 3.75), where participants were embodied in their current body. There were 5 sessions. In Session 1, participants completed a baseline assessment. There were then 2 VR exposures, approximately 1 week apart (Sessions 2‐3), and follow-ups at 1 week (Session 4) and approximately 2 weeks (Session 5) after the final VR exposure. Outcomes included subjective age, awareness of age-related change, World Health Organization–Five Well-Being Index, Trail Making Test performance, and physical functioning (eg, grip strength). Results: A hierarchical Bayesian analysis revealed that 1 week after the final VR exposure, those in the Young Self condition demonstrated lower subjective age than those in the Current Self condition (prob=.95). They had higher awareness of positive age-related change (prob=.89) and a higher score on the World Health Organization–Five Well-Being Index (prob=.84). Moreover, with respect to performance variables, they took less time to trace a trail (prob≥.99), made fewer mistakes in doing so (prob=.89), had greater right-hand (prob=.85) and left-hand (prob≥.99) grip strength. However, 2 weeks after their final VR exposure, these differences diminished apart from positive awareness of age-related change (prob=.82), trail-making mistakes (prob=.83), and left-hand grip strength (prob≥.99). Here, “prob” refers to posterior probability. Conclusions: The results demonstrate that even 2 short VR exposures, where people were embodied in their younger body and immersed in an iconic event from more than 50 years earlier, resulted in improvement in some age-related responses. This is encouraging for further research with more extensive VR experiences over a longer time period.
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Effectiveness of a Fully Automated Mobile Therapeutic Versus a General Chatbot in Reducing Depression and Anxiety and Improving Well-Being: Feasibility Randomized Controlled Trial
Background: Given the increasing prevalence of depression and anxiety disorders and enduring barriers to care, there is a critical need for alternative treatment options. Generative artificial intelligence (AI) chatbots show promise for increasing access to mental health care, though more direct research is needed to establish their efficacy. Objective: This pilot study aimed to test the efficacy of a generative mental health chatbot rooted in solution-focused therapy compared to the general-purpose ChatGPT and an assessment-only control (AOC) group on depression, anxiety, and well-being. Methods: A total of 185 English-speaking adults were recruited online and randomly assigned to one of three groups: AI therapy, ChatGPT, or AOC. Of these, 147 eligible participants filled out a pretreatment assessment. Over a 3-week period, the AI therapy group (n=44) was instructed to complete 3 structured, fully automated app-based sessions per week (9 total), while the ChatGPT group (n=60) was instructed to engage in 9 unstructured conversations with ChatGPT (GPT-4o–based models). The control group (n=43) received no intervention. In the AI therapy group, 39% (n=17) completed all sessions, as did 62% (n=38) of those in the ChatGPT group. Primary outcome measures, self-assessed online at baseline and postintervention, included the Patient Health Questionnaire-9 (PHQ-9), Overall Depression Severity and Impairment Scale (ODSIS) (depression), 7-item Generalized Anxiety Disorder Scale (anxiety), and World Health Organization Well-Being Index (5-item version) (well-being). Linear mixed effects models were used for data analysis. Results: Compared to AOC, both the AI therapy group (=−0.47; =.01) and the ChatGPT group (=−0.44; =.02) demonstrated significant reductions in depression scores measured by PHQ-9. The AI therapy group showed nonsignificant reductions in anxiety (=−0.37; =.11) and ODSIS depression scores (=−0.25; =.22) and an increase in well-being (=0.12; =.53) compared to AOC. Similarly, a nonsignificant reduction in anxiety (=−0.27; =.22) and ODSIS depression scores (=−0.12; =.53) and an increase in well-being (=0.20; =.29) were observed in the ChatGPT group compared to AOC. The AI therapy group did not significantly outperform the ChatGPT group on any outcomes (PHQ-9: =−0.19; =0.03; =.87; 7-item Generalized Anxiety Disorder Scale: =−0.57; =−0.11; =.62; ODSIS: =−0.59; =−0.13; =.50; and WHO: =−0.38; =−0.07; =.69). Conclusions: Both the structured generative AI chatbot and ChatGPT showed a significant reduction in depression scores compared to the control group. No significant effects were observed across other outcomes, although descriptive trends indicated improvements in anxiety. While the AI therapy group showed descriptively better outcomes for depression and anxiety, differences between groups were not significant. A larger sample and longer intervention may be needed for the emerging trends to yield clinically meaningful effect sizes. Trial Registration: OSF Registries osf.io/r76ef;
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Brain Astrocytes Form Far-Reaching Connections in Mice
A study in mice headed by NYU Langone Health researchers has found that cells long thought to play a secondary role in brain function build their own far-reaching connections. These pathways appear to connect distant regions in ways that had not been mapped before.
Experts usually describe the brain as a network of nerve cells (neurons) that send each other signals to pass along information. These neurons are maintained by another kind of brain cell, the star-shaped astrocyte, which ferries in nutrients and carries away waste.
The newly reported study, headed by Melissa Cooper, PhD, a postdoctoral fellow in the department of neuroscience at NYU Grossman School of Medicine, revealed that, like neurons, astrocytes form organized webs, which enable them to communicate with other specific astrocytes across the brain rather than only sending local, generalized signals. In some cases, the pathways were found to link areas that were not already joined together by neurons.
“For more than a century, neuroscientists have thought of neurons as the main actors in the brain,” said Cooper. “Yet our findings suggest that astrocytes, which are usually viewed as merely support cells, are also running their own widespread signaling pathway, adding another layer to how brain regions stay connected.” The team suggests that while their study was carried out in mice, not humans, the findings form the basis for future studies investigating how astrocyte networks might link with injury, disease, or aging and to learning and memory.”
Cooper is first and co-corresponding author of the team’s published work in Nature, titled “Astrocytes connect specific brain regions through plastic networks,” in which the researchers stated, “Astrocyte networks can directly link brain regions that are not connected by neurons, suggesting that previously unassociated brain regions communicate with one another through gap junction-coupled astrocytes.”
“Neuronal axons have traditionally been considered to be the primary mediators of functional connectivity among brain regions,” the authors wrote, and the role of communication mediated by astrocytes has been largely underappreciated. “This communication occurs through gap junctions—membrane channels that connect the cytoplasm of neighboring cells, enabling them to redistribute resources and share biochemical signals,” the team continued. “Studies using mice lacking astrocyte gap junctions have shown that these gap junctions are necessary for memory formation, synaptic plasticity, coordination of neuronal signaling, and closing the visual and motor critical periods.”
In earlier work, Cooper reported that in a mouse model of the visual neurodegenerative disease glaucoma, astrocytes can redistribute resources from astrocytes around healthy neurons to damaged neurons. Yet the team had no way to see whether this kind of support-cell network extended across the entire brain.
Cooper said the newly reported study is the first to map active, brain-wide communication networks built by astrocytes and to show that these pathways are highly specific. The research relied on a custom-built tracing tool that let the team follow the cells’ connections in far greater detail than had been possible using past methods. “Despite the importance of astrocyte gap junctional networks, studying them has been challenging,” the investigators noted. “Current methods such as slice electrophysiology disrupt network connectivity and introduce artefacts due to tissue damage.”
For their study, the researchers used a harmless virus to deliver “network tracers” into astrocytes in selected brain regions of lab mice. These tracers tagged small molecules as the molecules passed through the gap junctions linking one astrocyte to another, allowing the team to see which cells were part of the same signaling pathway.
The scientists then made the mice’s brains transparent and used a specialized microscope to capture three-dimensional images of every tagged astrocyte. By doing this across hundreds of mice, they could map astrocyte webs across brain areas. “These networks selectively connect specific regions, rather than diffusing indiscriminately, and vary in size and organization,” they reported. “We observe local networks that are confined to single brain regions and long-range networks that robustly interconnect multiple regions across hemispheres, often exhibiting patterns distinct from known neuronal networks.”
![A 3D network of interconnected astrocytes imaged inside a whole, transparent mouse brain. Each astrocyte's color shows its distance from the viewer; closer astrocytes are blue, while more distant astrocytes are red. [Cooper et al. Astrocytes connect specific brain regions through plastic networks. Nature. 2026. doi:10.1038/s41586-026-10426-6.]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_Cover-Image-224x300.jpg)
The tracing tool and brain-clearing method were designed to be relatively low-cost and easy to reproduce so that other labs could use them to study the networks in many brain diseases.
In another part of the study, the team assessed mice that were genetically engineered with astrocytes that lacked gap junctions. The communication networks largely disappeared, suggesting that the pathways are active and depend on these physical bridges.
“By challenging our understanding of how the brain communicates over long distances, our results may offer fresh insight into how it develops, ages, and behaves in conditions such as Alzheimer’s and Parkinson’s diseases,” said study co-senior author Shane A. Liddelow, PhD, an associate professor in the neuroscience and ophthalmology departments at NYU Grossman School of Medicine.
Another key finding was that astrocyte networks are dynamic. When the team trimmed whiskers on one side of the mice’s faces—“this manipulation is known to induce robust structural remodeling in neurons,” the team noted—a pathway from the region that processes whisker touch got smaller and reconnected to different astrocyte partners.
“The fact that astrocyte networks shrink and reroute after a loss of sensory signals suggests they may be shaped by experience,” said study co-senior author Moses V. Chao, PhD, a professor in the cell biology, neuroscience, and psychiatry departments at NYU Grossman School of Medicine. “It also raises the possibility that each of us has a somewhat unique pattern of connections molded by what our brains have learned and lived through.”
The authors plan to investigate which molecules move through the networks and to apply their tracing tool to models of brain disorders. They also hope to examine how these webs change during development and aging, said Chao.
Liddelow emphasized that while gap junctions and astrocytes exist in humans, it remains unknown whether the networks link the same regions in the same way as in mice. Nevertheless, in their paper, the team concluded that their findings “… establish foundation for future exploration of how astrocyte network structure and function are shaped by injury, disease, development, aging and experience-dependent processes such as learning and memory.”
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<![CDATA[AFSP and JED plan a 2026 merger to form the largest US suicide prevention nonprofit, uniting research, youth mental health programs, advocacy, and community support.]]>
Breast Cancer Cell Metastatic State Characterized by Prrx1 Levels
A new study published in Nature Communications is reshaping how researchers think about metastasis, showing that the cells most likely to spread are not defined by extremes, but by a precise balance of biological states within the primary tumor.
The work, led by Raúl Jiménez Castaño, PhD, and colleagues in the Cell Plasticity in Development and Disease Laboratory headed by Ángela Nieto at the Instituto de Neurociencias in Spain, identifies a nonlinear relationship between expression of the transcription factor Prrx1 and metastatic potential in breast cancer. Tumors with intermediate levels of Prrx1—not low or high—were found to be the most metastatic.
“This is unusual,” Jiménez Castaño said. “You normally expect a linear correlation—either low or high expression being the most relevant. But here, the peak of metastasis is in the intermediate levels.”
From paradox to mechanism
The study builds on longstanding efforts to understand the epithelial-to-mesenchymal transition (EMT), a developmental program that enables cells to migrate and is co-opted by cancer cells during metastasis. While EMT has been widely linked to tumor dissemination, the new findings show that metastatic potential is not simply a function of how invasive a cell becomes. Instead, it depends on a finely tuned balance between invasion and proliferation—two processes that are often at odds.
Previous work from the group and others had produced conflicting results regarding the role of Prrx1. In some models, removing the gene reduced metastasis; in others, it appeared necessary for dissemination. To resolve this contradiction, the researchers turned to patient tumor samples, where they observed that metastatic incidence peaked in tumors with intermediate Prrx1 expression.
Modeling a metastatic “sweet spot”
To investigate, the team engineered mouse models with graded levels of Prrx1 expression, mimicking the spectrum observed in human tumors. The results closely mirrored patient data. Tumors lacking Prrx1 showed little ability to metastasize, while those with high expression were capable of invasion but produced relatively few metastases. In contrast, tumors with intermediate levels generated the highest metastatic burden.
At the invasive front of these tumors, the researchers identified a distinct population of cells capable of both migrating and adopting divergent fates—either proliferating or entering a dormant state. This balance proved to be the critical determinant of metastatic success.
To understand the underlying biology, the team applied a range of advanced techniques, including single-cell RNA sequencing, chromatin profiling, and spatial transcriptomics. These approaches allowed them to map cellular states within tumors and link Prrx1 expression levels to functional behavior.
The analyses revealed that Prrx1 plays a dual role: it promotes invasion while simultaneously activating a dormancy program that suppresses cell division.
“At the same time that Prrx1 is necessary for cancer cells to be invasive, it also activates a dormancy program,” Jiménez Castaño explained.
This creates a biological trade-off. At high Prrx1 levels, cells are highly invasive but largely non-proliferative, limiting their ability to form metastases. At low levels, cells retain proliferative capacity but cannot effectively disseminate. Only at intermediate levels do cells achieve both capabilities.
“If the cancer cell has these intermediate levels, it is both invasive and proliferative,” he said. “And therefore, these cells will create a lot of metastasis.”
Metastatic potential begins in the primary tumor
One of the study’s most significant implications is that metastatic potential is determined earlier than previously appreciated. Rather than being dictated solely by conditions at distant sites, the ability of cancer cells to form metastases appears to be encoded within specific cell states in the primary tumor.
“The big conclusion is that already in the primary tumor, the potential of the cancer cells to metastasize is defined,” Jiménez Castaño said.
This finding aligns with broader observations from the field that tumors contain heterogeneous populations of cells with distinct functional properties. In this case, a subset of cells with intermediate Prrx1 expression represents a particularly dangerous state—one that combines mobility with the capacity for sustained growth.
Implications for biomarkers and therapy
Although the study identifies Prrx1 as a potential marker of metastatic risk, translating this insight into clinical practice will require further validation. The researchers were able to stratify tumors into low, intermediate, and high expression groups using staining intensity and computational analysis, but defining precise thresholds remains a challenge.
“We cannot say at this moment it is a biomarker,” Jiménez Castaño noted.
Even so, the findings provide a conceptual framework for improving patient stratification and identifying tumors with a higher likelihood of metastasis.
They also suggest new therapeutic strategies. Rather than attempting to eliminate invasive behavior entirely, it may be possible to push tumor cells into states that are less capable of forming metastases. For example, maintaining high Prrx1 expression could promote invasion while simultaneously enforcing dormancy, preventing metastatic outgrowth.
The post Breast Cancer Cell Metastatic State Characterized by Prrx1 Levels appeared first on Inside Precision Medicine.
mRNA Uses Unconventional Pathways in CD8+T Cell Priming to Help Vaccines Work
mRNA vaccines scored a stunning win against SARS-CoV-2 in 2020, and now the Nobel-prize–winning technology is out to conquer some cancers. Several mRNA vaccines are already in clinical trials for melanoma, small cell lung cancer, and bladder cancer, among others. Recently, a pancreatic cancer vaccine grabbed headlines after researchers shared that most Phase I trial participants were still alive after several years—unprecedented in a disease that is considered incurable, and usually kills patients quickly.
But how exactly does mRNA work? A new study suggests a broader role for how T cells become activated after an mRNA vaccine. It’s a process that engages both cDC1 and cDC2 cells redundantly. The study was led by researchers at Washington University School of Medicine in St. Louis (WashU) and could lead to improvements in mRNA vaccine design. The findings were published in Nature. The work was powered by a novel mouse model developed by the WashU team.
“My lab made them in 2019 and 2022. We put all of them in Jackson labs [database] so anyone can get them, no strings, and study them,” senior author Kenneth M. Murphy, MD, PhD, told Inside Precision Medicine. “Thanks to them, we saw the question and were able to address it most quickly.”
Until now, scientists assumed that cDC1, which is a classical type 1 dendritic cell, was required for mRNA vaccination to activate the immune system. But, in a lab study, these researchers found that even without cDC1 cells, the mRNA vaccine still triggers strong cancer‑killing responses. That’s because they determined that cDC2, a cousin to cDC1, can also stimulate anti-tumor immune activity—an unexpected finding given that this related subtype is not involved in responses to other vaccines.
“There is a lot of interest in applying the mRNA vaccine approaches used during the COVID-19 pandemic to the problem of inducing anti-tumor immunity,” said Murphy, the Eugene Opie Centennial Professor in the department of pathology & immunology at WashU Medicine. “By dissecting which immune cells are involved and how they coordinate the response, we’re offering vaccine developers some additional mechanistic insights to consider in their goal of optimizing these vaccines against tumor proteins.”
Murphy is also a research member at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.
mRNA vaccines work by delivering instructions, in the form of messenger RNA, for immune cells to produce bits of protein that trigger the immune system to destroy cells bearing these proteins. Dendritic cells produce the protein bits from the mRNA instructions, and T cells then find and destroy the invading proteins. To treat cancer, mRNA vaccines can be designed to generate protein bits unique to a tumor.
The work was done in collaboration with the study’s co-corresponding author, William E. Gillanders, MD, the Mary Culver Professor of Surgery at WashU Medicine. Gillanders, a physician-scientist and surgical oncologist who has also developed an investigational vaccine against triple-negative breast cancer, treats patients at Siteman Cancer Center.
Murphy and members of his lab used their mouse models, which lacked cDC1 or cDC2, to tease out the role that different groups of dendritic cells play in priming T cells after mRNA cancer vaccination.
One of their findings was that mice immunized with an mRNA vaccine generated strong T-cell responses even in the absence of cDC1s. In addition, they found that immunized mice without cDC1s were able to clear sarcoma tumors—cancers that develop in connective tissues such as fat, muscle, nerves, blood vessels, bone, and cartilage. This indicated that some other cell type must be stimulating the T-cell response.
Indeed, their study found that cDC2s also participate in generating an immune response from T cells and preventing tumor growth. Further, the study found that T cells turned on by cDC1s and cDC2s each showed slightly different molecular “fingerprints.” These differences could help scientists design better versions of vaccines in the future.
Similarly, immunized mice lacking cDC2s and mice that had both cell subtypes produced an immune response and rejected tumor growth, demonstrating that mRNA vaccination uses both dendritic cell subtypes to stop cancer.
“This work uncovers a new way mRNA vaccines engage the immune system—through both cDC1 and cDC2—which helps explain their power and gives researchers concrete targets for making future mRNA cancer vaccines more effective,” said Gillanders. “It could improve vaccine formulation and dosing, potentially explain why some patients respond better to vaccines than others, and guide strategies for making vaccines more effective.”
The post mRNA Uses Unconventional Pathways in CD8+T Cell Priming to Help Vaccines Work appeared first on Inside Precision Medicine.
STAT+: At AACR, talk of Chinese biotech, oncology’s comms issue, and more
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Overcoming resistance and RevMed’s next drug?
In case you missed it, Revolution Medicines’ sessions yesterday were jam-packed with conference attendees. While most of the media coverage focused on the daraxonrasib in frontline pancreatic cancer data, the company also revealed some activity in a new compound, RM-055. CEO Mark Goldsmith described it as being part of a new class of “catalytic inhibitors,” since it can slice off a phosphate from GTP-RAS, or the “on” form of RAS, and turn the protein off.
This generated a lot of interest because one of the main ways that cancer develops resistance to RAS inhibitors is by amplifying mutant RAS, basically flooding the cell with the oncoprotein and overwhelming the inhibitor. RM-055, with its catalytic ability to turn multiple mutant RAS proteins off, may be the next step in the arms race against RAS-addicted cancer.
Andelyn Partners with S. Korea-Based ENCell to Accelerate Global Delivery of Gene Therapies
Andelyn Biosciences and ENCell, both CDMOs, signed a collaboration agreement to create a strategic manufacturing bridge between the United States and Asia-Pacific (APAC) regions to accelerate the global delivery of gene therapies.
The partnership leverages both companies’ GMP manufacturing facilities, technical expertise, and regional networks to fast-track the development, manufacturing, and global expansion of client programs, according to officials at both organizations.
This partnership is designed to enable a streamlined “dual hemisphere” workflow. By providing a direct route between U.S. and APAC manufacturing hubs, the collaboration could help remove a number of the regulatory and logistical complexities of international expansion.
Most importantly, facilitating in-country manufacturing for in-country clinical trials ensures regional supply chains can meet the specific needs of local patient populations, greatly reducing lead times and accelerating the path to commercialization, pointed out Wade Macedone, CEO at Andelyn.
“Our partnership with ENCell is a powerful step forward in Andelyn’s mission to help bring life-saving therapies to patients worldwide,” he said. By joining forces with such a respected leader in South Korea, we are not just expanding our global footprint; we are leveraging our unique strengths to deliver a truly seamless international manufacturing network.”
“This partnership with Andelyn represents a significant step in expanding the global CGT ecosystem,” added Jong Wook Chang, PhD, CEO of ENCell. “By combining Andelyn’s expertise in viral vector development and cGMP manufacturing with ENCell’s clinical and manufacturing capabilities across APAC, we are establishing a seamless manufacturing platform connecting the United States and Asia-Pacific.
“Together, we will enable more efficient development and scalable production of gene therapies, supporting our clients from early-stage development through global clinical trials and commercialization.”
The post Andelyn Partners with S. Korea-Based ENCell to Accelerate Global Delivery of Gene Therapies appeared first on GEN – Genetic Engineering and Biotechnology News.
Video: Robert F. Kennedy Jr. testifies before Senate HELP committee
Health secretary Robert F. Kennedy Jr. testified on Wednesday before the Senate lawmakers who arguably hold the most power in advancing or hindering his Make America Healthy Again agenda.
The Senate Health, Education, Labor, and Pensions Committee hearing put the secretary face-to-face with Chair Bill Cassidy (R-La.), whose vote to confirm Kennedy last year came with a number of promises on vaccine policy that Kennedy has since blown through.
Presurgery Pembrolizumab May Be the Future for Some Operable CRCs
Groundbreaking data from the Phase II NEOPRISM-CRC trial show that patients given pembrolizumab prior to surgery for certain types of high-risk, operable colorectal cancer (CRC) remain relapse-free for almost three years.
Furthermore, the response to treatment can be predicted by DNA and T cell biomarkers.
At present, the standard of care for people with high-risk stage II or III CRC with deficient DNA mismatch repair (dMMR) or microsatellite instability (MSI), like those included in the study, is surgery followed by chemotherapy, but relapse rates can range from 15% to 40% at three years.
Pembrolizumab is already given to patients with inoperable stage IV dMMR/MSI CRC to shrink the tumors and prolong life, but it is not yet available for patients with operable tumors.
The NEOPRISM-CRC trial investigated whether pembrolizumab could benefit such patients.
For the study, 32 people with large, high-risk stage II or III dMMR/MSI CRC were given three cycles of intravenous pembrolizumab 200 mg followed by surgery.
The researchers, led by Kai-Keen Shiu, from University College London (UCL) Cancer Institute, have previously reported that that 59% of participants had a pathologic complete response (pCR) to pembrolizumab, indicating that there were no cancer cells in tissue samples removed from these patients during surgery.
The data presented at the American Association for Cancer Research Annual Meeting 2026 by Yanrong Jiang, a PhD student at UCL Cancer Institute, focused on survival outcomes and whether biomarkers could predict which patients respond to pembrolizumab.
She reported that, after a mean of 33 months of follow-up, all patients were alive and relapse-free.
Shiu said: “Seeing that no patients have experienced a cancer recurrence after almost three years of follow-up is extremely encouraging and strengthens our confidence that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk bowel cancers.”
Blood samples taken throughout the study were assessed for circulating tumor (ct)DNA using the highly sensitive whole genome tumor-informed Personalis NeXT Personal assay, which can track up to 1800 patient-specific variants.
The team found that all 25 patients with evaluable data had detectable ctDNA at baseline.
Remarkably, after one round of treatment with pembrolizumab, 24% of participants no longer had detectable ctDNA. The proportion increased to 43% and 58% after rounds two and three, respectively. Post-surgery, ctDNA was undetectable in all 25 patients.
When the researchers analyzed the ctDNA clearance profiles, they identified three distinct patterns. They designated the first group “super molecular responders.” All six patients in this group had undetectable ctDNA after one cycle of pembrolizumab.
The “dynamic molecular responder” group included 11 patients who cleared ctDNA at different rates—four after cycle two of pembrolizumab, five after cycle three, and the remainder post-surgery, even though the level was decreasing rapidly during immunotherapy.
The final group, termed “poor molecular responders,” included eight patients who showed stable, high levels of ctDNA throughout immunotherapy, with levels only becoming undetectable post-surgery.
Interestingly, the pCR rate varied across the three groups: It was 100% among the super molecular responders and 82% among the dynamic molecular responders, but 0% among the poor molecular responders.
Shiu told Inside Precision Medicine that measuring ctDNA using the Next Personal assay could “potentially trump all standard tests when it comes to informing decision making.”
He suggested that the super molecular responders could potentially consider forgoing surgery altogether, while the poor molecular responders could be considered for treatment intensification, such as the addition of a second immunotherapy agent.
Although ctDNA gives information on how the tumor is responding to treatment, it doesn’t explain why some patients respond and others don’t.
The researchers, therefore, also carried out T cell receptor (TCR) sequencing, which provides a readout of the immune environment within the tumor, specifically whether there are expanded T cell populations that may recognize cancer, explained Marnix Jansen, MD, a clinician scientist and consultant histopathologist who led the translational research on the trial from UCL Cancer Institute.
“We found that patients who achieved a complete response had a higher proportion of expanded T cell clones in their tumors, suggesting a more focused and effective anti-tumor immune response at baseline,” he said.
When the team combined the ctDNA results with the TCR sequencing data, they improved the ability to predict outcomes compared with using either biomarker alone.
“The key implication is that integrating immune and tumor biomarkers in a dynamic model may allow early, data-driven treatment decisions, such as identifying patients who are highly likely to benefit or, conversely, those who may need a change in therapy,” Jansen told Inside Precision Medicine.
The post Presurgery Pembrolizumab May Be the Future for Some Operable CRCs appeared first on Inside Precision Medicine.