The Philippines faces a staggering cancer burden, with nearly 189,000 new cases and over 113,000 deaths recorded in 2022, according to the International Agency for Research on Cancer (IARC). This local crisis mirrors a global trend, with IARC projecting a 77% surge in new cases worldwide by 2050, reaching over 35 million annually. In the Philippines, the 2025 National Cancer Summit reports more than 180,000 new diagnoses each year, with the disease claiming an estimated over 300 Filipino lives every day.
A Molecular Defense Against Cancer's Spread
In response to this escalating health emergency, researchers from the University of the Philippines–Diliman are pioneering a novel molecular approach. Chemists Christian Angelo Concio and Dr. Susan Arco from the UPD College of Science’s Institute of Chemistry (UPD-CSIC), collaborating with Dr. Wen-Shan Li's team in Taiwan, have designed new compounds to combat cancer metastasis, the process by which cancer spreads.
Their work focuses on creating lithocholic acid-3,3′-diindolylmethane (LCA-DIM) hybrids. These compounds are engineered to block the activity of enzymes called sialyltransferases (STs). "These hybrids work by stopping the enzyme known as sialyltransferase, the key enzyme for the sialylation process," Concio explained. This process, known as hypersialylation, is a stealth tactic where cancer cells coat themselves with excessive sialic acid to hide from the body's immune system and facilitate their progression.
Targeting Precision and a Tough-to-Treat Cancer
The study specifically targeted two ST enzymes: ST6GAL1 and ST3GAL1. While both are implicated in cancer, they are often overexpressed in different cancer types. A significant finding was the new hybrids' selective inhibition of ST6GAL1 over ST3GAL1. "This selectivity is ideal for next-generation ST inhibitors," Concio noted, as it could lead to more precise therapies with fewer side effects.
Critically, the LCA-DIM hybrids demonstrated effectiveness in inhibiting the spread of triple-negative breast cancer (TNBC) cell lines. TNBC is an aggressive subtype known for being particularly difficult to treat due to its lack of common hormone receptors, making this discovery a promising avenue for future therapy development.
A Different Path from Traditional Chemotherapy
The research builds on previous knowledge about indole compounds and their anticancer potential. By hybridizing an "indole-rich" compound (DIM) with a known ST inhibitor scaffold (LCA), the team created a more potent and selective agent. This mechanism offers a distinct advantage over conventional treatments.
"Unlike traditional anticancer drugs such as doxorubicin, which directly kill cancer cells but often cause severe side effects and face drug resistance, our ST inhibitor works through a different mechanism," Concio said. "It targets cancer metastasis, aiming to block the spread of cancer cells rather than just destroy them, thereby helping to slow disease progression and make cancer treatment more manageable."
The team's next steps involve advancing the research toward clinical application, including testing the safety, stability, and efficacy of the hybrids in animal models. While the current study centered on breast cancer, the scientists plan to explore its potential in other cancers with high ST6GAL1 levels, such as pancreatic and ovarian cancers.
Their groundbreaking paper, titled "Novel lithocholic acid-diindolylmethane hybrids as potent sialyltransferase inhibitors targeting triple-negative breast cancer: a molecular hybridization approach," is published in the esteemed journal RSC Medicinal Chemistry.
