New Approaches Target Cancer Proteins and Immune Disease Pathways

A research team led by Prof. Ki-Young Lee at the College of Medicine, Sungkyunkwan University, has uncovered a previously unrecognized tumor-intrinsic role of the immune checkpoint molecule PD-L1, providing new mechanistic insight into lung cancer progression. PD-L1 (Programmed death-ligand 1) has been widely known for its role in helping tumors evade immune surveillance by suppressing anti-tumor immune responses. However, emerging evidence suggests that PD-L1 may also regulate intracellular signaling pathways within cancer cells.

By integrating transcriptomic analyses of patient-derived non-small cell lung cancer (NSCLC) datasets with functional and molecular experiments, Prof. Lee's research team demonstrated that PD-L1 acts as a critical regulator of autophagy and metastasis-related signaling networks within tumor cells. Using CRISPR-Cas9-mediated gene editing and protein interaction analyses, the researchers identified a novel molecular mechanism in which PD-L1 directly regulates autophagy signaling.

PD-L1 depletion in lung cancer models resulted in reduced cell proliferation, decreased migration and colony-forming capacity, and suppressed tumor growth and metastasis in xenograft models. These findings demonstrate that tumor-intrinsic PD-L1 plays a functional role in cancer progression beyond its canonical immune regulatory activity. The study was published online on February 18, 2026, in the international journal Experimental Hematology & Oncology.

In a separate advance in drug discovery, teams led by Georg Winter (Scientific Director at the AITHYRA Research Institute for Biomedical Artificial Intelligence and Adjunct Principal Investigator at the CeMM Research Center for Molecular Medicine in Vienna, Austria) and Michael Erb (Associate Professor at the Scripps Research Institute in La Jolla, California, U.S.A.) developed a new method to systematically discover molecular glues. These small molecules induce interactions between proteins that would not normally bind to each other, allowing disease-causing proteins to be brought into contact with cellular degradation enzymes and selectively eliminated by the cell itself.

Starting from a small molecule that already binds to a target protein, the researchers generated thousands of chemical variants by systematically attaching different molecular building blocks. Each variant subtly reshapes the surface of the protein, potentially enabling new protein–protein interactions. These compounds were screened directly in living cells, without prior purification, using a sensitive assay that reports whether the target protein is being degraded. This enabled rapid identification of active compounds from a vast chemical space.

As a proof of principle, the researchers focused on ENL, a protein that plays a central role in certain forms of acute leukemia. From several thousand tested compounds, the team identified a molecule that efficiently and selectively triggers degradation of ENL in leukemia cells. The compound primarily affects ENL and downstream gene programs controlled by this protein, leading to a strong reduction in the growth of ENL-dependent leukemia cells.

The compound acts through a cooperative mechanism characteristic of molecular glues. Rather than binding strongly to all interaction partners, it first binds ENL and then creates a new interaction surface that recruits a cellular ubiquitin ligase, which marks ENL for degradation. The study was published in Nature Chemical Biology on 16 February 2026.

Meanwhile, advances in understanding immune-mediated inflammatory diseases (IMIDs) are reshaping approaches to conditions like inflammatory bowel disease (IBD), rheumatoid arthritis, and psoriasis. IBD, which affects around 10 million people globally, is one example. With chronic inflammation and unpredictable flares, the condition illustrates how complex IMIDs can be.

Despite advances, IBD remains a condition defined by uncertainty for patients and physicians alike. The causes are complex, symptoms can vary dramatically, and what works well for one person may not for another. Currently, determining the right medication often comes down to "trial and error," and even when symptoms improve, long-term remission isn't guaranteed. Recent research suggests that roughly one in four people with IBD require surgery within 10 years of diagnosis, underscoring the need for more durable, targeted, less invasive options.

Research aimed at using multiple drugs or addressing multiple targets with one medicine may help achieve stronger, more durable results. Through the integration of genetics, biomarkers, and clinical data, research teams are aiming to embed precision medicine across every phase of drug development, starting in early research.