Penetrium Bioscience has announced new scientific evidence demonstrating, for the first time at the cellular level, the underlying mechanism behind the long-standing ‘Seed & Soil’ theory originally proposed by Stephen Paget in 1889. The findings reveal how pathological tumour microenvironments (soil) fundamentally limit the efficacy of targeted therapies—and how Penetrium’s novel approach overcomes this barrier.
The data, presented ahead of the company’s participation at AACR 2026, introduce a mechanism that directly addresses the long-standing challenge of sub-lethal drug exposure, a key driver of therapeutic resistance in oncology.
For decades, oncology drug development has focused primarily on targeting cancer cells (seed) through genetic and molecular pathways. However, new findings presented by Penetrium Bioscience demonstrate that the true origin of resistance lies in the tumour microenvironment (soil), which prevents drugs from reaching effective cytotoxic concentrations.
“The central flaw in modern oncology has been the assumption that resistance originates within the cancer cell itself,” said Jinho Choy, keynote presenter of a scientific symposium held at the National Press Club in Seoul.
“In reality, the tumour microenvironment creates a protective barrier that reduces drug exposure to sub-lethal levels—triggering adaptive resistance.”
Penetrium’s mechanism directly targets this barrier. By modulating pathological macrophages and cancer-associated fibroblasts (CAFs), the therapy disrupts the tumour’s protective ecosystem, enabling co-administered therapies to achieve full lethal concentrations at the tumour site.
This approach not only enhances therapeutic efficacy but also prevents the emergence of adaptive resistance at its source.
The findings were independently validated through collaborative studies conducted by Seoul National University Hospital and KAIST (Korea Advanced Institute of Science and Technology). These studies confirmed that Penetrium’s observed effects in pathological models are fully consistent with prior RNA sequencing (RNA-seq) data derived from pancreatic cancer organoids.
This alignment provides evidence that Penetrium’s mechanism is not limited to a specific tumour type, but rather represents a broadly applicable platform for microenvironment normalisation across multiple cancers.
A critical implication of this research is the resolution of the “sub-lethal dose” dilemma—where insufficient drug exposure leads to incomplete tumour killing and subsequent resistance.
By dismantling the tumour’s physical and biological defence systems, Penetrium enables therapies to reach effective lethal concentrations. This eliminates the conditions that foster adaptive resistance, enhances the durability of existing targeted therapies, and potentially restores efficacy to drugs limited by resistance.
“Penetrium is not designed to compete with existing therapies, but to unlock their full potential,” said Won-Dong Cho, chairman and CEO of Penetrium Bioscience.
“We see significant opportunities to partner with global pharmaceutical companies to restore and extend the value of targeted therapies that have been constrained by resistance.” The company is actively pursuing strategic collaborations with global biopharma partners to integrate Penetrium into combination therapy regimens across oncology indications.