Researchers have identified a small but powerful group of pancreatic cancer cells that are responsible for resistance to gemcitabine, the most commonly used chemotherapy for the disease. These cells, known as cancer stem cells, are marked by high levels of a protein called ARPC1B. Unlike other tumor cells, they can survive treatment and regenerate the tumor. Patients whose tumors have high ARPC1B levels tend to have more aggressive disease and shorter survival.
Further analysis showed that ARPC1B-positive cancer stem cells have strong self-renewal ability and high genetic instability, carrying more cancer-driving mutations. This makes tumors more diverse and harder to eliminate with standard drugs. These cells appear to act as the source of chemotherapy resistance, allowing cancer to return even after initial treatment.
To counter this, researchers identified a small molecule called CK-636 that can directly bind to and block ARPC1B. When CK-636 was combined with gemcitabine, resistant tumor cells became sensitive to treatment again. Tests in patient-derived tumor models and mice showed much smaller tumors compared with chemotherapy alone. The findings suggest that targeting ARPC1B alongside standard treatment could help overcome drug resistance and improve outcomes for pancreatic cancer patients.