Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies

The pathogenesis of cancer represents a multifaceted, progressive process driven by an intricate interplay of physical, chemical, biological, and other etiological factors. Recent advancements in clinical oncology, including targeted therapy, surgical resection, radiation therapy, chemotherapy, and immunotherapy, have substantially improved patient outcomes. Targeted therapy has emerged as a promising approach due to its precision and minimal adverse effects. Pyruvate kinase M2 (PKM2) is a metabolic enzyme with protein kinase function that has been extensively studied for its critical role in inflammation and metabolic diseases. By interacting with key oncogenic signaling pathways, PKM2 exerts a critical influence on cancer progression, thereby establishing its status as a potential therapeutic target for cancer. Notably, the role of PKM2 in cancer is not determined solely by expression level but also depends on post-translational modifications, conformational plasticity, nuclear localization, and tumor microenvironment. Extensive preclinical studies have demonstrated that various natural products and compounds exert antitumor effects by modulating PKM2 activity and expression, conformation, or nuclear localization. However, these strategies have not yet entered the clinical trial phase, and the path to clinical application remains fraught with challenges, including the biological complexity of PKM2, tumor resistance, and drug specificity. In summary, this article summarizes the regulatory network between PKM2 and oncogenic signaling pathways, highlights the importance of PKM2 in current clinical strategies for cancer treatment, and discusses the challenges facing therapies targeting PKM2 as well as future research directions.