Enhancing Ovarian Cancer Management through PKM2 Proteoformics

Role of Pyruvate Kinase M2 in Ovarian Cancer Progression

Ovarian cancer (OC) represents a significant global health challenge, with recent statistics indicating that approximately 324,398 new cases are diagnosed annually worldwide, leading to around 206,839 deaths. The disease often manifests at advanced stages, complicating treatment and significantly reducing the five-year survival rate, particularly for high-grade serous carcinoma (HGSC), which can drop to as low as 30%. One crucial metabolic player in OC is pyruvate kinase M2 (PKM2), which is a key enzyme in the glycolytic pathway. PKM2 is known to be overexpressed in various tumors, including OC, and is involved in metabolic reprogramming that supports cancer cell proliferation and survival.

The PKM gene encodes two isoforms: PKM1 and PKM2. PKM2 is predominantly expressed in high-proliferation cells, such as cancer cells, and its expression is associated with enhanced glycolytic flux, leading to increased lactate production—an indicator of the Warburg effect. This metabolic shift allows cancer cells to thrive in low-oxygen environments, facilitating their malignant characteristics, including epithelial to mesenchymal transition (EMT), which is critical for metastasis. Moreover, the ratio of PKM1 to PKM2 is altered in cancerous tissues compared to normal tissues, with PKM2 being the predominant isoform in OC, thereby serving as a potential therapeutic target (Wang et al., 2025).

Table 1: PKM2 Characteristics and Functions in Ovarian Cancer

The Impact of Metabolic Reprogramming on Tumor Behavior

Metabolic reprogramming is a hallmark of cancer that allows tumor cells to adapt to their microenvironment and sustain continuous proliferation. The Warburg effect, where cancer cells favor glycolysis over oxidative phosphorylation (OXPHOS) even in the presence of sufficient oxygen, is a prime example of this phenomenon. This metabolic adaptation results in the accumulation of lactate, which not only fuels further metabolic pathways but also acidifies the tumor microenvironment, promoting immune evasion and tumor progression.

In OC, lactic acid produced through glycolysis serves as an immunomodulatory compound that can alter the behavior of various immune and stromal cells within the tumor microenvironment (TME). For instance, lactic acid can induce a shift in tumor-associated macrophages (TAMs) from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, which further supports tumor proliferation and metastasis. Glycolytic enzymes, including PKM2, play a pivotal role in regulating this metabolic reprogramming, thereby influencing the tumor’s behavior and response to therapy.

Key Glycolytic Enzymes in Ovarian Cancer

Predictive, Preventive, and Personalized Medicine in Oncology

The integration of predictive, preventive, and personalized medicine (PPPM) in oncology presents a comprehensive strategy for managing OC. This approach utilizes genetic, proteomic, and metabolic biomarkers to identify individuals at high risk for developing OC, facilitating early detection and intervention. Genetic predispositions, such as mutations in BRCA1 and BRCA2, alongside metabolic profiles that highlight alterations in glycolytic pathways, offer opportunities for tailored therapies.

Recent advancements in biomarker research have led to the identification of over 100 protein biomarkers for clinical diagnosis, treatment monitoring, and recurrence evaluation in OC. However, many of these biomarkers suffer from insufficient specificity and sensitivity, necessitating the need for more precise and reliable markers. PKM2 proteoformics offers a promising avenue for developing specific biomarkers that can improve the accuracy of diagnoses and treatment strategies.

Table 2: Overview of Biomarkers in Ovarian Cancer

Significance of Tumor-Infiltrating B Lymphocytes in HNSCC

Tumor-infiltrating B lymphocytes (TILBs) play a critical role in the immune response to tumors, including head and neck squamous cell carcinoma (HNSCC). Their presence within the tumor microenvironment has been associated with better prognostic outcomes, as they can enhance T cell activation and promote the formation of tertiary lymphoid structures (TLS). These structures facilitate the organization of immune cells, leading to improved antitumor responses.

Recent studies have highlighted the importance of identifying TILB-related signatures as potential prognostic tools in HNSCC. Gene expression profiles of TILBs have shown promise in predicting patient outcomes and responses to immunotherapy. The ability to quantify TILB infiltration within tumors provides valuable insights into the tumor’s immunological landscape, further supporting the development of personalized treatment strategies.

Table 3: Prognostic Impact of Tumor-Infiltrating B Lymphocytes

Innovations in Drug Delivery Systems for CNS Diseases

Advancements in drug delivery systems, particularly for central nervous system (CNS) diseases, are paramount due to the challenges posed by the blood-brain barrier (BBB). Lipid nanoparticles (LNPs) have emerged as a promising solution for delivering therapeutic agents across this barrier. By encapsulating drugs within lipid-based formulations, researchers can enhance bioavailability and target specific CNS tissues more effectively.

Recent innovations in LNP design focus on improving their stability, circulation time, and targeting capabilities. Surface modifications with specific ligands allow for enhanced uptake by brain endothelial cells, facilitating transcytosis and improving drug delivery to the CNS. These advancements in LNP technology represent a significant stride towards effective treatments for neuroinflammation and other CNS disorders.

Table 4: Characteristics and Benefits of Lipid Nanoparticles

Reference

1. Wang, Y., Xu, N., Ndzie, N. M. L., Chen, L., & Zhan, X. (2025). Pyruvate Kinase M1/2 Proteoformics for Accurate Insights into Energy Metabolism Abnormity to Promote the Overall Management of Ovarian Cancer Towards Predictive, Preventive, and Personalized Medicine Approaches. Metabolites, 15(3), 203. https://doi.org/10.3390/metabo15030203
2. Qin, Y., Zheng, Z., Liu, D., Sun, S., Zhao, X., & Lv, L. (2025). Role of Furfural and 5-Methyl-2-furfural in Glucose-Induced Inhibition of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Formation in Chemical Models and Pork Patties. Molecules, 30(6), 1254. https://doi.org/10.3390/molecules30061254
3. Zhang, M., Sun, Q., Yao, Y., Chen, X., Li, J., Yuan, T., Mou, Y., & Li, Y. (2025). Identification of a Prognostic Signature Based on Tumor-Infiltrating B Lymphocyte mRNA in Head and Neck Squamous Cell Carcinoma. Journal of Immunology Research, 2025, 937588. https://pubmed.ncbi.nlm.nih.gov/11944952/
4. Abdelsalam, A. M., Balash, A., Khedr, S. M., Amin, M. U., Engelhardt, K. H., & Bakowsky, U. (2025). Improved Photodynamic Therapy of Hepatocellular Carcinoma via Surface-Modified Protein Nanoparticles. Pharmaceutics, 17(3), 370. https://doi.org/10.3390/pharmaceutics17030370
5. Zou, Y., Zhang, J., Chen, L., Xu, Q., Yao, S., & Chen, H. (2025). Targeting Neuroinflammation in Central Nervous System Diseases by Oral Delivery of Lipid Nanoparticles. Pharmaceutics, 17(3), 388. https://doi.org/10.3390/pharmaceutics17030388

FAQ

What is PKM2 and why is it important in ovarian cancer?

PKM2 is a key enzyme in the glycolytic pathway that is frequently overexpressed in ovarian cancer. Its activity is crucial for metabolic reprogramming, allowing cancer cells to grow and proliferate under low-oxygen conditions.

How does metabolic reprogramming affect tumor behavior?

Metabolic reprogramming, particularly the Warburg effect, enables cancer cells to produce energy through glycolysis rather than oxidative phosphorylation, which supports rapid cell growth and contributes to tumor aggressiveness.

What is the predictive, preventive, and personalized medicine approach?

This approach integrates genetic, proteomic, and metabolic data to identify high-risk individuals for early detection of diseases like ovarian cancer, allowing for tailored treatment strategies based on individual patient profiles.

How do tumor-infiltrating B lymphocytes influence cancer prognosis?

Tumor-infiltrating B lymphocytes play a significant role in the immune response against tumors. Their presence is often associated with better patient outcomes and can indicate a more effective immune response to cancer.

What advancements are being made in drug delivery systems for CNS diseases?

Innovations in lipid nanoparticles (LNPs) are being developed to enhance the delivery of therapeutic agents across the blood-brain barrier, improving bioavailability and targeting precision for treatments of CNS diseases.