Hyundai ADM Biotech has announced significant preclinical results for Penetrium, its first-in-class pseudo-resistance-targeting agent, demonstrating remarkable anti-metastatic efficacy in triple-negative breast cancer (TNBC). The detailed findings will be presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting in Chicago, beginning April 25.
The preclinical study, conducted by specialized CRO NodCure using seven-week-old female C57BL/6 mice, revealed striking differences between conventional treatment and the novel combination approach. Paclitaxel monotherapy achieved only a modest 4.55% tumor reduction compared to untreated controls, while alarmingly increasing metastasis by 115.13% (P<0.0001). In contrast, the combination of paclitaxel with Penetrium demonstrated superior efficacy, reducing tumor size by 36.22% (P<0.0001) and decreasing metastasis by 85.78% (P<0.001).
Addressing the Challenge of Pseudo-Resistance
A critical limitation of conventional cancer treatments is the development of pseudo-resistance, where repeated chemotherapy leads to stiffening of the extracellular matrix (ECM), progressively reducing drug effectiveness. Penetrium's innovative mechanism targets this specific barrier by softening the therapy-hardened ECM, effectively restoring access for both anticancer drugs and immune cells.
This approach represents a paradigm shift in cancer treatment strategy. Rather than directly targeting cancer cells, Penetrium modifies the tumor microenvironment itself, simultaneously addressing primary tumors and metastatic lesions while preventing further metastasis by blocking the formation of pre-metastatic niches.
"Penetrium introduces an innovative anticancer strategy, neutralizing ECM barriers that block effective drug and immune cell access to tumors," explained Soo-Jung Kim, Head of Drug Development at Hyundai ADM. "This preclinical outcome could be the world's first practical demonstration reversing the belief that metastatic cancer is untreatable."
Preventing Metastasis Through Niche Inhibition
Pre-metastatic niches—specialized microenvironments in distant organs that facilitate future metastatic growth—represent a critical challenge in cancer treatment. These niches develop through ECM remodeling, angiogenesis, increased vascular permeability, and immune suppression, creating hospitable conditions for circulating tumor cells.
Penetrium's ability to inhibit the formation of these niches represents a significant advancement in preventing metastasis, as it blocks the essential groundwork required for metastatic cells to successfully colonize new sites.
Consistent Results Across Cancer Types
The TNBC findings build upon previous research demonstrating Penetrium's efficacy in other aggressive cancers. A separate 2024 preclinical study on non-small cell lung cancer (NSCLC) showed a complete prevention of metastasis (0% metastasis rate) when Penetrium was combined with bevacizumab. Immunohistochemistry analysis confirmed the suppression of metastasis-promoting molecules MMP-9 and VEGF exclusively in the combination therapy group, validating Penetrium's mechanism of anti-metastatic action.
Addressing Unmet Needs in TNBC Treatment
Triple-negative breast cancer remains one of the most aggressive metastatic cancers worldwide, with limited treatment options. Current approaches, including antibody-drug conjugates and targeted therapies such as bevacizumab, face significant limitations, including minimal survival extension and ECM-induced drug delivery failures.
TNBC is characterized by the absence of estrogen receptors, progesterone receptors, and HER2 protein, making it unresponsive to hormonal therapies or HER2-targeted treatments. This aggressive subtype accounts for approximately 10-15% of all breast cancers and is associated with higher rates of metastasis and poorer prognosis compared to other breast cancer subtypes.
Future Development and Partnership Opportunities
Following these promising results, Hyundai ADM is expanding Penetrium-based clinical strategies for breast and lung cancers. Meanwhile, Hyundai Bioscience is focusing on applications for pancreatic, prostate, and bile duct cancers. Both companies plan to actively pursue global licensing and co-development partnerships following their presentations at the AACR Annual Meeting.
The potential implications of Penetrium's mechanism extend beyond the specific cancer types studied thus far. By addressing the fundamental challenge of drug delivery through the extracellular matrix—a common barrier across many solid tumors—this approach could potentially transform treatment paradigms for multiple cancer types characterized by aggressive metastasis and poor response to conventional therapies.
