Cell Biology

New Study Suggests Cancer Research Has an Age Problem

Posted on by Kelly Grooms
White lab mouse among test tubes overlaid with a blue DNA helix.

Most cancer research relies on young, healthy mice. Most cancer patients are not young. Could this disconnect between model organism and patient, which ignores the impact of the physiological realities of aging, explain why some therapies perform well in the lab but not in clinical trials? Focusing on lung cancer, a study published in Nature investigated what happens when these two realities, young and old, finally meet in the lab (1). The answers could reshape how we think about cancer research and the impact of aging on metastasis and disease progression.

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Before the First Dose

Posted on by Elise Johnson

Kierkegaard observed that one of humanity’s enduring tensions is that while life can only be understood backwards, it must be lived forwards. It’s a truth medicine knows intimately: in the treatment that worked until it didn’t, the resistance that arrived without warning, the moment a doctor has to tell a patient that the drug that was helping has stopped. Not because anyone made a mistake, but because the critical knowledge that would have mattered arrived too late, if at all.

A recent paper from the National Cancer Institute is, in a small but meaningful way, science’s pursuit of that elusive foresight: an understanding that emerges early enough, for once, to change what happens next.

The Elegant Idea

For decades, chemotherapy has worked by brute force, flooding the body with toxins designed to kill rapidly dividing cells. The problem is that rapid division isn’t unique to cancer. Hair follicle cells, gut lining cells and immune cells also divide rapidly, which is why patients lose hair, lose energy and become susceptible to infection. Chemotherapy targets a behavior, but the drug has no way to tell a healthy cell from a cancerous one.

Antibody-drug conjugates (ADCs) change that. Instead of targeting what cancer cells do, they target what cancer cells are. Cancer cells tend to display certain proteins on their surface in far greater numbers than healthy cells do. The antibody is engineered to seek out those proteins specifically. It navigates to its target, binds and waits for the cell to do what cells routinely do: pull it inside. Once there, the cell’s own digestive machinery (the lysosome) breaks down the chemical tether holding the toxin to the antibody, releasing the toxin to kill the cell from within. More than a dozen ADCs have received FDA approval in recent years, and the field is evolving fast.

What the Cell Does Next

But cancer cells don’t simply accept their fate. Even when an ADC delivers its payload perfectly—the antibody finds its target, the cell pulls it inside, the lysosome cuts the tether—a pump embedded in the cell membrane can grab the released toxin and throw it back out before it causes damage.

The delivery worked. The package got ejected anyway.

These pumps—ATP-binding cassette transporters, or more plainly, efflux pumps—are a normal feature of cell biology. Their job is cellular housekeeping, clearing out unwanted or toxic substances before they cause damage. Under the pressure of drug treatment, cancer cells do what life has always done under pressure: the ones best equipped to survive do. The same mechanism that has shaped living things for billions of years now works against the treatment. Not all cancer cells are identical, and the ones that happen to produce more pumps survive while others don’t, gradually shifting the tumor toward resistance.

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Detecting Neuroinflammation in Microglia and Astrocytes

Posted on by Simon Moe

The brain is one of the most complex and fascinating parts of biology. Thankfully, it’s also remarkably good at protecting itself. When exposed to a pathogen, an injury or even misfolded proteins, microglia and astrocytes function as the central nervous system’s (CNS) primary immune defenders. They mount an inflammatory response by releasing cytokines and working to contain the damage. Yet this same system can malfunction or not resolve, which manifests as devastating consequences.

Chronic neuroinflammation is now recognized as a shared characteristic across some of the most common and difficult-to-treat neurological conditions. A 2023 review in Signal Transduction and Targeted Therapy highlighted the dualistic nature of neuroinflammation: while acute responses serve a protective role, chronic or dysregulated inflammatory signaling can initiate and accelerate neurodegeneration, identifying these pathways as priority targets for therapeutic intervention (Zhang et al., 2023). A 2025 review in Science reinforced this view, noting that within Multiple Sclerosis, disease-modifying therapies targeting neuroinflammation have seen the most clinical success (Shi & Yong, 2025). This could suggest applications within neurological conditions where the same inflammatory mechanisms are at work.

Understanding how and where these inflammatory signals originate in the CNS is an active area of preclinical research. One cytokine being actively studied is IL-6. IL-6 is produced by several cell types, including astrocytes and microglia in the CNS. As a key mediator of inflammatory responses, it mediates pro-inflammatory effects through its trans-signaling, which occurs via soluble IL-6 receptors. Dysregulation of this mechanism may contribute to the chronic neuroinflammation seen in several neurological conditions. Characterizing how and when IL-6 is secreted from CNS cells is an important step toward understanding the neuroinflammatory processes underlying these disorders.

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Why BRETSA™ Target Engagement Matters for Drug Discovery

Posted on by Michele Arduengo, PhD

Drug discovery researchers face a fundamental constraint in their work to develop safe, effective therapeutics: the vast majority of the human proteome remains inaccessible to conventional small molecule approaches. Proteins without defined binding pockets, those lacking known chemical probes, and protein targets that fail to translate from biochemical assays into cellular models have long been considered out of reach of standard drug discovery screening tools. As Dixit et al. describe, developing biochemical or cellular assays for all genome-encoded targets “is not scalable and likely impossible as most proteins have ill-defined or unknown activity” — these are what the authors call “the dark undruggable expanses” of the proteome [1].

That gap is now narrowing. Promega Corporation recently launched the TarSeer™ BRETSA™ Target Engagement System, a live-cell target engagement platform designed to bring previously challenging targets within reach of early-stage drug discovery.

The Problem: A Translation Gap in Early Discovery

Drug discovery teams regularly encounter a frustrating disconnect. A compound may show strong binding activity in a biochemical assay, only to fail when tested in a cellular environment. Without target-specific cellular assays, which generally aren’t available for poorly characterized proteins, researchers face difficult choices when deciding which compounds to advance through the drug development pipeline.

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Your Media Choice Might Be Designing Your T-Cell Fate

Posted on by Simon Moe

Why Metabolism Matters in T-Cell Expansion

Adoptive T-cell therapies rely on generating metabolically fit, functional cells during ex vivo expansion—but this process often pushes T cells toward highly glycolytic, terminally differentiated states that limit their persistence and therapeutic potential. These metabolic programs begin shifting within hours of activation, therefore understanding early metabolic remodeling is essential for designing culture conditions that support durable, cytotoxic, and memory-enriched T-cell populations.

Researchers at Promega set out to address this challenge by systematically mapping how media composition and activation strength shape T-cell metabolism during the first 72 hours after stimulation. Using a suite of bioluminescent assays, they profiled intracellular energy cofactors, redox balance, and extracellular metabolites across several conditions. This approach revealed distinct, media-driven metabolic states that not only emerged early but also predicted downstream expansion, proliferation, and cytotoxic function.

Their work demonstrates how integrating metabolic profiling into in vitro expansion workflows can provide a more informed framework for optimizing T-cell manufacturing strategies.

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Residence Time: The Impact of Binding Kinetics on Compound-Target Interactions

Posted on by Promega

This blog was written by guest contributor Tian Yang, Associate Product Manager, Promega, in collaboration with Kristin Huwiler, Manager, Small Molecule Drug Discovery, Promega.

During the development of chemical probes or small-molecule drugs, compound affinity (Kd) or potency (IC50) is used to characterize compound-target interactions, to guide structure-activity relationship analysis and lead optimization and to assess compound selectivity.

However, neither parameter provides information on how quickly a compound engages with and dissociates from the target. The dissociation constant Kd reflects the relative concentrations of unbound and bound state of the compound at thermodynamic equilibrium, and while IC50 is an empirical metric that measures the concentration at which a biochemical or cellular process is reduced to half of the maximum value, IC50 values are typically determined when the process is assumed to be at equilibrium or steady-state. For a closed system, like cells in a culture dish, these thermodynamic parameters are quite informative. In an open system like the human body, where compound-target interactions often do not reach equilibrium, the kinetic parameters, in addition to the thermodynamic parameters, are needed to better understand and characterize compound target engagement over time (1,2).

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How Calcium Shapes Cell Communication and Invasion

Posted on by Shannon Sindermann

Platelets are best known for their role in blood clotting, but they also participate in other biological processes that influence how cells communicate and behave. In research models, scientists have observed that tumor cells can interact with platelets in ways that affect how they move and attach to new environments. A recent study by Morris et al., published in Scientific Reports, explored the molecular details behind these platelet–cell interactions and the role of calcium in regulating them.

The Role of Integrins and Calcium

The study focused on integrins, which are surface proteins that help cells anchor to their surroundings and communicate with the extracellular matrix. Two integrins, αIIbβ3 and αvβ3, are particularly important because they mediate platelet–platelet and platelet–cancer cell binding. Their structure and function depend on divalent cations such as calcium, which stabilize receptor conformation and support ligand binding.

When extracellular calcium levels were manipulated, platelet behavior changed in distinct ways.

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Insights from 3D Liver Models: Rethinking Fatty Liver Disease with Hormone Correction

Posted on by Simon Moe

Liver disease is a global health challenge, affecting millions each year. The liver has a remarkable ability to regenerate; however, chronic damage arising from obesity, alcohol, or metabolic dysfunction can lead to irreversible failure. At the University of Edinburgh’s Centre for Regenerative Medicine, Professor David Hay’s lab is developing innovative ways to study liver function and disease using a lab-grown mini-organ. In this blog, we highlight how Dr. Hay’s lab is redefining liver disease research through 3D models that reveal how hormones influence metabolic health.

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What Drives Muscle Fiber Shifts in Obesity and Type ll Diabetes?

Posted on by Kari Kenefick

Skeletal muscle is the body’s main consumer of glucose derived from food.

Muscle Fiber Types
Skeletal muscle is composed of two types of muscle fiber: Type I (slow-twitch) and Type II (fast-twitch).
Type I fibers contract slowly and can maintain contraction over long periods of time. They are rich in mitochondria and myoglobin and are well vascularized. These fibers rely mostly on aerobic metabolism to make the ATP that fuels cells. Type I muscle fibers are fatigue-resistant and efficient—great for supporting posture, distance running, cycling and any activity that needs steady output.

Type II fibers contract quickly, produce more force and power, but also fatigue more quickly. They have fewer mitochondria and less vasculature and rely more on anaerobic pathways like glycolysis (using glucose without oxygen).

Type I muscle fibers are smaller in diameter and generate less peak force but excel at endurance and heat management. Type II fibers are typically larger, produce more force and speed and handle explosive tasks like sprinting, jumping or heavy lifting.

Most muscles are a mix of fiber types, and genetics sets the starting ratio of Type l to Type ll, but fibers are adaptable. With aging and disuse, Type II fibers tend to atrophy more, which is one reason that power declines faster than endurance.

Another distinction important for this story: Type I fibers are more insulin-sensitive than Type II fibers. Additionally, these fiber types differ in different body types.

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Cellular Selectivity Profiling: Unveiling Novel Interactions and More Accurate Compound Specificity

Posted on by Promega

This blog was written by guest contributor Tian Yang, Associate Product Manager, Promega, in collaboration with Kristin Huwiler, Manager, Small Molecule Drug Discovery, Promega.

Determining the selectivity of a compound is critical during chemical probe or drug development. In the case of chemical probes, having a clearly defined mechanism of action and specific on-target activity are needed for a chemical probe to be useful in delineating the function of a biological target of interest in cells. Similarly, optimizing a drug candidate for on-target potency and reducing off-target interactions is important in the drug development process (1,2). A thorough understanding of the selectivity profile of a drug can facilitate drug repurposing, by enabling approved therapeutics to be applied to new indications (3). Interestingly, small molecule drugs do not necessarily require the same selectivity as a chemical probe, since some drugs may benefit from polypharmacology to achieve their desired clinical outcome.

Selectivity profiling panels based on biochemical methods have commonly been used to assess compound specificity for established target classes in drug discovery and chemical probe development. Biochemical assays are target-specific and often quantitative, enabling direct measurements of compound affinities for targets of interest and facilitate comparison of compound engagement to a panel of targets. As an example, several providers offer kinase selectivity profiling services using different assay formats and kinase panels comprised of 100 to 400 kinases (4). However, just as biochemical target engagement does not always translate to cellular activity, selectivity profiles based on biochemical platforms may not reflect compound selectivity in live cells (5).

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