Radically different
Cancer drugs can shrink fast-growing tumors. But sometimes a few tumor cells survive. These “persister” cells seed new tumors, forcing cancer patients into arduous cycles of testing and treatment. The problem is that persister cells are rare—as few as one in a thousand tumor cells—and they’re genetically identical to the tumor, which makes them hard to find. Plus, their tenacity can be temporary, and by the time a scientist can get them in a petri dish, the qualities that helped them survive may have faded.
To figure out how to beat them, researchers at the University of California, San Francisco (UCSF), built a robotic system that treats thousands of mini tumors at once in the laboratory. Their resulting ResMap platform lets scientists systematically identify, track, and treat surviving cells. The platform revealed shared features among persister cells that could help explain why cancer comes back—features that could be exploited by future drug therapies to beat them. “A few years ago, people were still asking whether persister cells were real,” said Xiaoxiao “Vany” Sun, PhD, an assistant researcher in the UCSF Department of Pharmaceutical Chemistry. “Now we can find them and test ideas for how to eliminate them.”
Sun is first author of the team’s published paper in Science Advances, titled “ResMap: A community resource for systematic mapping of therapy-persistent residual cancer cell dependencies across contexts,” stating, “ResMap establishes a foundation for coordinated community efforts to accelerate rational persister-directed combination strategies toward the clinic.”
Residual disease following targeted therapy remains a key challenge to achieving lasting responses in oncogene-driven cancers, the authors stated. Drug-tolerant persister cells, which the team describes as “subpopulations that survive initial therapy without stable genetic resistance,” can contribute to residual disease and seed tumor relapse. “Targeting drug-tolerant persister cells has emerged as an essential complement to oncogene-directed therapy, yet the field has lacked a unified framework to evaluate and prioritize candidate targets,” they wrote. “Understanding and targeting these cells have emerged as a promising strategy for achieving lasting therapeutic outcomes.”
Cancer cell persistence was first described in 2010, the authors explained, and studies have linked persister survival to different biological processes and resulted in “an expanding list” of candidate therapeutic targets. However, they noted, “… despite over a decade of research, no persister-directed therapy has reached clinical approval.”
For their reported study, the team gathered 94 drug candidates that other laboratories had flagged as potential persister therapies. They wanted to test each drug at different doses, on persisters from two types of lung cancer that had been treated with standard therapies. “As a testbed, we selected four lung cancer models: two with EGFR inhibitor osimertinib (EGFRi)–treated EGFRmut cell lines (PC9 and MGH134) and two with KRAS inhibitor sotorasib (KRASi)–treated KRASG12C cell lines (LU65 and MGH1138-1),” they wrote in summary. Each model was screened under normal oxygen and hypoxic conditions.
It would require 10,000 painstaking, week-long experiments—so they built a robotic platform to eliminate the labor and inconsistency of doing it by hand.
Thousands of miniature tumors sat in stacks of 384-well plates inside controlled incubators. A robotic arm, like those used in pharmaceutical drug screening, moved the plates between experimental stations. One station used sound waves to deposit tiny, precise doses of drug onto each tumor (first, a lung cancer therapy; then, an experimental persister therapy). Other stations stained the tumors with antibodies and took microscopic images of each tumor or group of persisters.
The overall ResMap platform incorporated multiple components, the team explained. “… we developed the ResMap platform incorporating four integrated components: an automated high-throughput workflow, machine learning-based normalization, a persistence-specific metric, and a validated framework.”
Their results showed that of the tested drugs, nine consistently weakened persister cells. The findings suggest that persister cells may share common vulnerabilities, even if they had emerged under different treatment conditions. “Initial screening identified 12 targets with conserved anti-persister activity across genotypes and oxygen environments; follow-up validation reproduced nine of these targets and revealed variable degrees of persister specificity relative to general cytotoxicity.” The investigators suggested that, “Collectively, these findings suggest that although persister biology involves multiple adaptive programs, targeting individual, well-chosen survival pathways may be sufficient to meaningfully reduce residual disease burden.”
Steve Altschuler, PhD, professor of pharmaceutical chemistry at UCSF and co-senior author of the paper, said, “We expected each tumor to behave as its own special case. Instead, we found patterns that held up across many different samples, suggesting there may be underlying rules that can help predict which therapies are most likely to work.”
The team plans to expand the platform to include more tumor types and treatment conditions. They hope the resulting dataset will be a resource to help researchers eliminate persister cells before they can give rise to drug-resistant disease. “ResMap provides a community resource for coordinated validation efforts and rational combination design aimed at minimizing residual disease following anticancer therapy,” they stated.
The post Therapy-Resistant Residual Cancer Cell Dependencies Mapped appeared first on GEN – Genetic Engineering and Biotechnology News.
Ultrasmall fluorescent core‑shell silica nanoparticles—best known for their roles in medical imaging applications—are now showing surprising therapeutic muscle. Originally engineered as inert carriers for imaging agents, these particles, called Cornell Prime dots (C’ dots), have steadily expanded their résumé. In a new preclinical study, researchers at Weill Cornell Medicine report that these engineered silica nanoparticles can directly kill prostate tumor cells while reawakening antitumor immunity, offering a potential new edge in a disease where immunotherapy has historically struggled.
Prostate cancer remains one of the most immunologically “cold” solid tumors, with myeloid‑driven immune suppression, metabolic bottlenecks, and stromal remodeling that blunt the effects of checkpoint blockade. The new work suggests that C’ dots—when targeted to prostate‑specific membrane antigen (PSMA)—can break through these layers of resistance by triggering ferroptosis, remodeling the tumor microenvironment, and priming tumors for combination immunotherapy.
“We’re very encouraged by these results; a treatment that directly induces tumor‑cell death while transforming the immune microenvironment, as this does, would represent a new clinical paradigm,” said senior author Michelle Bradbury, MD, PhD, the endowed professor of imaging research in radiology and director of the Molecular Imaging Innovations Institute at Weill Cornell Medicine and a neuroradiologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The study, published in Cancer Research and titled “Reprogramming of TLR–Ferroptosis Signaling and Immunometabolic Pathways Overcomes Myeloid Suppression to Improve Checkpoint Blockade in Prostate Cancer,” shows that the silica particles accumulate in prostate tumors and push cancer cells toward ferroptosis, a form of iron‑dependent cell death driven by runaway lipid peroxidation. Although the particles were originally designed for imaging, the team found that they often pick up positively charged iron ions in the bloodstream and shuttle them into tumor cells—effectively turning the particles into catalytic seeds for oxidative collapse.
At the same time, the nanoparticles reshape the immune landscape. T cells, macrophages, and other immune populations shift from inert or suppressive states into robust antitumor activity, converting cold tumors into hot ones. “One of the most intriguing aspects of this work is the convergence of direct tumor cell killing with broad immune remodeling,” said co‑author Jedd Wolchok, MD, PhD, the Meyer director of the Sandra and Edward Meyer Cancer Center, professor of medicine at Weill Cornell Medicine, director of the Parker Institute for Cancer Immunotherapy at Weill Cornell Medicine Meyer Cancer Center, and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The therapeutic impact was most striking in survival experiments. C’ dots alone modestly extended survival in aggressive mouse models, as did checkpoint blockade alone. But the combination produced complete or near‑complete remissions in 40% of mice. Adding CSF‑1R blockade increased complete remissions to 50%.
The researchers’ next steps include continuing to explore these ultrasmall core-shell silica particles, setting the stage for the platform’s translational potential.
“By creating conditions that support a more effective antitumor immune response, these particles may help unlock the full potential of immunotherapy in prostate cancer, where durable responses have historically been difficult to achieve,” added Wolchok.
The post Silica Nanoparticles Induce Ferroptosis, Reprogram Immunity in Prostate Cancer Models appeared first on GEN – Genetic Engineering and Biotechnology News.
Background: The mortality rate from liver disease among people with type 2 diabetes mellitus (T2DM) increased by 20% between 2001 and 2018. There are marked racial and ethnic differences among people with T2DM at risk of metabolic dysfunction–associated steatotic liver disease (MASLD) and related complications. Objective: We aimed to investigate the distribution of individual-level social determinants of health (SDOH) in people living with both T2DM and MASLD. Methods: In this small cross-sectional study, patients (N=50) were recruited from a tertiary care general hepatology clinic to complete a survey that assessed potential determinants of health. We sought to oversample Black and Hispanic patients to better understand the prevalence of SDOH. Electronic health records were reviewed to determine stage of liver disease, and these data were linked to survey results to identify the distribution of individual-level determinants of health in patients with cirrhosis. Results: Black and Hispanic respondents were more likely to report more experiences of racial discrimination, worries about being discriminated against, and group-based medical mistrust, especially regarding unsupportive health care providers. Cirrhosis groups tended to have lower incomes and less coverage from private health insurance. However, no substantial trends were observed in the distribution of health literacy, discrimination, and diabetes stigma among patients with and without cirrhosis. Conclusions: These findings will inform a future study aimed at assessing and developing interventions to address the combined impact of individual- and neighborhood-level SDOH on health-related outcomes in patients with T2DM and MASLD.
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With over a decade of hands-on experience in the biopharmaceutical industry, Victoria specializes in the design and implementation of ready-to-use solutions and single-use consumables supporting downstream purification processes. She brings a strategic, highly collaborative approach to problem-solving, partnering closely with cross-functional teams to deliver scalable improvements that enhance operational efficiency and drive successful results.
Victoria is passionate about building strong team environments, supporting diverse learning styles, and applying data-driven decision-making to optimize performance across the process lifecycle.
With more than 30 years of leadership experience in the biopharmaceutical and life sciences industries, Cole specializes in manufacturing operations, supply chain strategy, and MSAT across the product lifecycle. He brings a strategic, results-driven approach to operational excellence, partnering with cross-functional teams to optimize manufacturing performance, strengthen supply reliability, and support successful commercialization.
Cole is passionate about building high-performing organizations, developing talent, and leveraging data-driven decision-making to drive continuous improvement, scalability, and business growth.
Downstream bottlenecks often stem from early process design decisions that fail to fully account for scale, variability, and the manufacturing realities of therapeutic modalities such as monoclonal antibodies.
As upstream titers rise and novel modalities introduce added complexity, these early oversights can force reactive workarounds that impact throughput, cost, and product quality. By taking a more deliberate and forward-looking approach, teams can reduce downstream risk and build processes that are better equipped for manufacturing scale.
In this GEN webinar, our speakers will examine five common planning gaps that can contribute to bottlenecks, including single-source material dependency, raw material pack size selection, sensitive buffer designs, and single-use systems designed without realistic failure modes. Using real-world MSAT and tech transfer examples, they will illustrate how, when overlooked, these drivers can lead to deviations, safety risks, and longer cycle times—and how to proactively address them. The webinar explores practical strategies that can help evaluate materials, buffer systems, and consumables through a scale‑ready lens—helping teams build more robust purification processes and avoid these common bottlenecks.
A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.
Produced with support from:
The post When Process Design Fails: 5 Common Planning Gaps That Create Downstream Purification Bottlenecks appeared first on GEN – Genetic Engineering and Biotechnology News.
Officials at Leiden, Netherlands-based CRO ZoBio say the company has launched a DNA-Encoded Library (DEL) discovery service, which is designed to help biotech and pharmaceutical companies generate validated, progressible hits against novel and challenging drug targets.
The new offering combines structure-grade protein production, quantitative biophysics, DEL screening, off-DNA hit validation and X-ray crystallography into a single workflow, according to a company spokesperson, who explains that it enables clients to move beyond hit identification toward high-confidence starting points for drug discovery programs.
ZoBio maintains that unlike transactional DEL screening approaches that focus solely on hit generation, its platform is designed to deliver biologically relevant, structurally characterized hit matter with clear potential for progression. The service is particularly suited to exploratory and difficult-to-drug targets, including protein–protein interactions (PPIs) and targets with poorly defined binding pockets, where conventional screening approaches often fail, notes Gregg Siegal, CEO of ZoBio.
“Drug discovery teams today are increasingly focused on highly validated but technically challenging targets, where traditional screening approaches can struggle to deliver meaningful starting points,” he continues. “Our approach combines DEL technology with the structural biology, biophysics, and assay expertise needed to generate hits that clients can confidently progress.”
Siegal also points out that the DEL service is library-agnostic, enabling clients to access commercially available DEL collections or apply ZoBio’s workflow to proprietary client-owned libraries. The integrated platform reportedly includes:
The workflow is designed to support collaborative decision-making throughout the discovery process, helping clients rapidly establish whether difficult or exploratory targets are viable for further development, according to Siegal, who says that members of the ZoBio team will be available for meetings during the BIO International Convention in San Diego to discuss the new service.
The post ZoBio Introduces DNA-Encoded Library Service for Exploratory Drug Discovery Programs appeared first on GEN – Genetic Engineering and Biotechnology News.
Background: Although patient outcomes are improved by stroke rehabilitation, the suggested amount of therapy is rarely maintained. The COVID-19 pandemic aggravated this situation further due to disruptions in health care. One solution was the rapid and extensive transition to virtual care. A hybrid outpatient stroke telerehabilitation program (HOSTP) was introduced by St John’s Rehab—a tertiary rehabilitation hospital in Toronto, Ontario. The HOSTP integrated in-person and virtual care in an effort to alleviate long-standing obstacles that challenge stroke rehabilitation. Objective: This study explored health care providers’ (HCPs) experiences with the HOSTP and their perspectives on its implementation, quality, and impact to determine the modifications needed to optimize its delivery and sustainability. Methods: A qualitative implementation study was conducted, with semistructured interviews conducted among HCPs involved in the HOSTP. The interview guide was informed by the CFIR (Consolidated Framework for Implementation Research). In total, 14 HCPs were recruited and interviewed from St John’s Rehab outpatient program. Interview transcripts were analyzed using a 2-stage analytic approach involving inductive thematic analysis, followed by deductive categorization using CFIR. Results: Four main themes were identified across CFIR domains: (1) adaptability and flexibility of the hybrid care model (intervention characteristics), (2) alignment with patient needs and resources (outer setting), (3) the impact of organizational resources and infrastructure (inner setting), and (4) variability in provider confidence and perceptions of virtual care (characteristics of individuals). Key determinants were identified as adaptability, patient-related factors, resource availability, and provider beliefs about virtual care. Conclusions: Our findings suggest that, from HCPs’ viewpoints, optimizing virtual care processes and resources may support access and care quality within hybrid outpatient stroke rehabilitation. HCPs viewed maintaining virtual care as important for supporting ongoing access and patient-centered care. Lastly, optimizing the benefits and mitigating the drawbacks of hybrid care can ensure future integration of virtual care into standard outpatient stroke rehabilitation.
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