Even when a promising medicine reaches a tumor, another obstacle can arise: cancer cells often adapt to hostile conditions to survive. One key challenge is hypoxia, or low oxygen levels, which are common inside solid tumors. Researchers at Macau University of Science and Technology created 19-dihydrocalotoxin, a cardiac glycoside derived from calotoxin modifications. Instead of only targeting cancer cell destruction, this approach also aims at HIF-1, a protein that helps cancer cells adapt to low oxygen environments. The patent states that 19-dihydrocalotoxin reduces HIF-1α protein levels under hypoxia. Laboratory tests showed activity against cancer cell lines such as colon, lung, and breast cancers. Importantly, they assessed the balance between anticancer effects and toxicity to normal cells, a critical issue for cardiac glycosides. Results indicated lower toxicity in normal cell models compared to related compounds. The compound was also tested in mice with breast tumors, showing greater tumor growth inhibition than paclitaxel at the same doses. Images and measurements on page 13 confirm smaller tumors with 19-dihydrocalotoxin and reduced HIF-1α expression in tissue analyses. These are preclinical findings, not proven in patients. They highlight that reaching the disease might not be enough, the treatment must also counteract the biological survival mechanisms within the tumor.
When cancer adapts to survive, can a medicine target its survival strategy?
Patent number: CN 112194703 B
Inventor(s): L. Bai, Z. Zheng, X. Zhou, G. Zhu, and Z. Jiang
Citation: L. Bai, Z. Zheng, X. Zhou, G. Zhu, and Z. Jiang, “一种强心苷类化合物及其合成方法与应用 [A cardiac glycoside compound and its synthesis method and application],” China Patent CN 112194703 B, Aug. 3, 2021.
