Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Area of Science:

• Oncology
• Cancer Biology
• Drug Discovery

Background:

• Current cancer treatments often achieve initial tumor regression but frequently fail due to cancer relapse.
• Recurrent cancers are typically resistant to subsequent therapies, highlighting the need for novel treatment strategies.
• Cancer cell heterogeneity, particularly the presence of stemness-high cancer cells, contributes to treatment resistance, metastasis, and relapse.

Purpose of the Study:

• To investigate the efficacy of BBI608, a novel small molecule inhibitor, against cancer stem cells.
• To determine if targeting cancer stemness can prevent cancer relapse and metastasis.

Main Methods:

• BBI608 was tested for its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties.
• The drug's effect on stemness gene expression, spherogenesis, and survival of stemness-high cancer cells was evaluated.
• The impact of BBI608 on cancer relapse and metastasis was assessed in preclinical mouse models.

Main Results:

• BBI608 successfully inhibited stemness gene expression and demonstrated cytotoxic effects on stemness-high cancer cells from various cancer types.
• The small molecule BBI608 effectively blocked cancer relapse and metastasis in mouse models.
• These findings indicate BBI608's potential in targeting cancer stemness.

Conclusions:

• Targeting cancer stemness represents a novel therapeutic strategy to overcome treatment resistance and prevent cancer recurrence.
• BBI608 shows promise as a next-generation cancer therapeutic agent for suppressing cancer relapse and metastasis.
• Further development of BBI608 could significantly advance cancer medicine by addressing critical unmet needs in managing advanced disease.