Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
Author
Summary, in English
Abnormal vascularization of solid tumours results in the development of microenvironments deprived of oxygen and nutrients that harbour slowly growing and metabolically stressed cells. Such cells display enhanced resistance to standard chemotherapeutic agents and repopulate tumours after therapy. Here we identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues. The anticancer activity is associated with reduced mitochondrial respiration, leading to bioenergetic catastrophe and tumour cell death. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. Importantly, VLX600 displays tumour growth inhibition in vivo. Our findings suggest that tumour cells in metabolically compromised microenvironments have a limited ability to respond to decreased mitochondrial function, and suggest a strategy for targeting the quiescent populations of tumour cells for improved cancer treatment.
Department/s
- Division of Translational Cancer Research
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2014
Language
English
Publication/Series
Nature Communications
Volume
5
Issue
Feb 18
Links
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Cancer and Oncology
Status
Published
ISBN/ISSN/Other
- ISSN: 2041-1723