Cancer stem cells (CSCs), considered as the “seeds” of cancer. Although CSCs are rare cells within a tumor (approximately 1% within the bulk tumor mass), the frequent failure in trying to treat advanced cancers using the current standard of care therapies has been attributed to the presence of CSCs as these cells actively resist all methods of treatment, including chemotherapy and radiotherapy.

The current invention can increase K+/H+ flux on the mitochondrial and lysosomal membranes which disrupts mitochondrial and lysosomal functions leading to apoptosis. It is reported that some CSCs have higher dependence on oxidative phosphorylation (OXPHOS) in mitochondria for energy production (in contrast, cancer cells favour the glycolysis pathway for metabolism). As a result, this kind of CSCs are more sensitive toward mitochondrial stress induced by current invention.

Fig. 1: Schematic diagram of the underlying mechanism

The compound candidates can reduce the tumor-forming ability of ovarian CSCs in mice (in contrast, paclitaxol may induce more ovarian CSCs at certain concentration).

Fig. 2. In vivo tumor-forming ability of HEYA8 CSCs treated as indicated

mean ± SEM, n = 4 mice per group, **p < 0.01

• Drugs for anti-cancer stem cells, especially in ovarian and liver cancer
• Combination chemotherapy for reducing cancer recurrence

Patents

• US provisional: No. 62/939,803
• US provisional: No. 62/940,601

IP Status

• Provisional patent