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Targeting STAT3 and oxidative phosphorylation in oncogene-addicted tumors
Matilda Lee1, Jayshree L Hirpara2, Jie-Qing Eu2
1Department of Haematology-Oncology, National University Health System, Singapore; Haematology-Oncology Research Group, National University Cancer Institute of Singapore, National University Health System, Singapore.
Redox Biology
|December 31, 2018
Summary
Targeting signal transducer and activator of transcription 3 (STAT3) and oxidative phosphorylation (OXPHOS) offers new hope for overcoming drug resistance in oncogene-addicted cancers. Strategies focus on restoring sensitivity by inhibiting these key pathways.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Drug resistance in oncogene-addicted cancers limits targeted therapy effectiveness.
- Upregulation of signal transducer and activator of transcription 3 (STAT3) is a known resistance mechanism.
- Emerging evidence links metabolic reprogramming, specifically oxidative phosphorylation (OXPHOS), to cancer cell survival and drug resistance.
Purpose of the Study:
- To review the roles of STAT3 and OXPHOS in cancer drug resistance.
- To explore novel therapeutic strategies targeting STAT3 and OXPHOS.
- To discuss the potential for restoring drug sensitivity in resistant tumors.
Main Methods:
- Literature review of STAT3 signaling and cancer metabolism.
- Analysis of therapeutic strategies targeting STAT3 and OXPHOS.
- Discussion of challenges and future directions in drug development.
Main Results:
- STAT3's mitochondrial localization may link signaling pathways to cancer metabolism.
- Repurposed drugs (metformin, phenformin) and novel compounds show anti-cancer activity by inhibiting OXPHOS.
- STAT3 inhibitors face challenges with delivery, specificity, and toxicity.
Conclusions:
- Targeting STAT3 and OXPHOS represents a promising therapeutic avenue for overcoming drug resistance.
- Further research is needed to develop compounds with favorable toxicity profiles and robust biomarkers.
- Transforming cancer cell metabolism offers a new frontier in cancer treatment.
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