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Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies
Jiaxing Wang1,2, Wenyu Zhang1, Nana Shen1
1Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, Xi'an, 710069, China.
The AAPS Journal
|June 2, 2026
Summary
Pyruvate kinase M2 (PKM2) is a key metabolic enzyme influencing cancer progression. Targeting PKM2 offers a promising cancer therapy strategy, but challenges like tumor resistance and drug specificity need further research.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer pathogenesis involves complex etiological factors.
- Recent oncology advancements improve patient outcomes.
- Targeted therapy shows promise with precision and fewer side effects.
Purpose of the Study:
- To summarize the regulatory network between PKM2 and oncogenic signaling pathways.
- To highlight PKM2's importance in cancer treatment strategies.
- To discuss challenges and future directions for PKM2-targeted therapies.
Main Methods:
- Review of preclinical studies on PKM2 modulation by natural products.
- Analysis of PKM2's role in cancer progression via signaling pathways.
- Summary of regulatory mechanisms including post-translational modifications and localization.
Main Results:
- PKM2 plays a critical role in cancer progression by interacting with oncogenic signaling pathways.
- PKM2's function is influenced by expression, post-translational modifications, conformation, localization, and tumor microenvironment.
- Natural products show antitumor effects by modulating PKM2, but clinical translation is limited.
Conclusions:
- PKM2 is a potential therapeutic target for cancer.
- Challenges remain in clinical application due to PKM2's complexity, tumor resistance, and drug specificity.
- Further research is needed to overcome these challenges for effective PKM2-targeted therapies.
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