Enhancing Cancer Treatment with Nanomaterials in Starvation Therapy

Overview of Cancer Starvation Therapy and Its Importance

Cancer remains one of the most challenging diseases, characterized by the uncontrolled growth of cells that invade surrounding tissues and can metastasize to distant organs. The World Health Organization (WHO) estimates that approximately 704,000 new cancer cases will occur in Brazil annually during the triennium 2023–2025. Recent studies attribute these increases to demographic changes and globalization, which have led to extended life expectancy and an aging population (1). Traditional cancer treatments, including surgery, chemotherapy, and radiation, often fail to provide long-lasting solutions due to issues such as drug resistance and significant side effects.

Starvation therapy is an innovative approach that focuses on depriving cancer cells of essential nutrients, thereby inhibiting their growth. This method can target the blood supply to tumors, obstruct nutrient delivery, and disrupt metabolic pathways crucial for cancer cell survival. Recent advancements in nanotechnology have enabled the development of multifunctional nanomaterials, which can enhance the effectiveness and precision of starvation therapy while minimizing side effects (2). By employing these nanomaterials, clinicians can improve drug delivery systems, facilitate targeted therapies, and ultimately enhance treatment outcomes for cancer patients.

Mechanisms of Action: Blood Occlusion and Metabolic Interventions

Cancer starvation therapy primarily utilizes two mechanisms: blood occlusion and metabolic intervention. Blood occlusion involves disrupting the tumor’s blood supply to deprive it of oxygen and essential nutrients. Various strategies, such as anti-angiogenesis agents and vascular disrupting agents, aim to inhibit the formation of new blood vessels and destroy existing ones. For example, agents like bevacizumab and combretastatin A4 have shown efficacy in clinical trials by targeting tumor vasculature (3).

On the other hand, metabolic interventions focus on depriving cancer cells of specific nutrients, such as glucose, amino acids, and lactate. Cancer cells often exhibit a dependency on these nutrients due to their altered metabolism, exemplified by the Warburg effect, where cancer cells preferentially utilize aerobic glycolysis even in the presence of oxygen. Strategies to inhibit glucose uptake can involve the use of glucose oxidase (GOx), which catalyzes the oxidation of glucose, generating hydrogen peroxide (H2O2) that can induce oxidative stress in tumor cells (4).

Table 1 summarizes the mechanisms of action in starvation therapy:

Role of Nanomaterials in Improving Delivery and Efficacy

Nanomaterials play a crucial role in enhancing the delivery and efficacy of starvation therapy. Their unique properties allow for improved targeting of cancer cells, reducing off-target effects and enhancing therapeutic outcomes. Superparamagnetic iron oxide nanoparticles (SPIONs) are of particular interest due to their ability to be directed to specific locations using magnetic fields, thereby minimizing systemic toxicity (5).

The incorporation of nanomaterials into starvation therapy enables the co-delivery of multiple therapeutic agents, improving the overall treatment efficacy. For example, combining glucose oxidase with nanoparticles can enhance the localized production of H2O2, amplifying the therapeutic effects of starvation therapy while simultaneously targeting cancer cells (6). Recent studies have demonstrated the effectiveness of multifunctional nanoparticles in delivering anti-cancer drugs while inducing starvation, showcasing their potential in clinical settings.

Table 2: Examples of Nanomaterials in Starvation Therapy

Challenges in Clinical Application of Starvation-Based Therapies

Despite the promising prospects of starvation therapy, several challenges hinder its clinical application. One major issue is the poor targeting ability of many starvation-inducing agents, which can affect healthy tissues and lead to adverse effects. The lack of specificity often allows tumors to develop alternative pathways for nutrient uptake, resulting in treatment resistance (7).

Additionally, the creation of a hypoxic environment within tumors can paradoxically promote the survival of more aggressive cancer cells, complicating treatment outcomes. The need for continuous and precise delivery of starvation therapies is essential to avoid systemic toxicity and ensure the effectiveness of treatment (8).

Moreover, the development of resistance to starvation therapies poses a significant barrier to long-term efficacy. Tumors can adapt rapidly to nutrient deprivation, making it imperative to explore combination therapies that integrate starvation with other treatment modalities, such as chemotherapy, immunotherapy, or radiation (9).

Future Directions: Multifunctional Nanoparticles in Cancer Treatment

The future of cancer treatment may lie in the continued advancement of multifunctional nanoparticles that integrate various therapeutic strategies. Current research is focused on developing nanoparticles capable of delivering multiple agents simultaneously, utilizing both starvation and traditional chemotherapy or targeted therapies to enhance treatment efficacy while minimizing side effects.

Additionally, ongoing studies are investigating the use of novel nanomaterials that can respond to specific tumor microenvironments, allowing for more precise targeting and controlled release of therapeutic agents (10). Innovations in this field hold the potential to revolutionize cancer treatment by improving patient outcomes and reducing the burden of adverse effects associated with conventional therapies.

Table 3: Promising Nanoparticle Developments

FAQ

What is cancer starvation therapy?

Cancer starvation therapy is a treatment strategy that aims to deprive cancer cells of essential nutrients, thereby inhibiting their growth and survival. This is achieved through mechanisms such as blood occlusion and metabolic interventions.

How do nanomaterials enhance cancer treatment?

Nanomaterials enhance cancer treatment by improving drug delivery, targeting specific tumor sites, and enabling the co-delivery of multiple therapeutic agents. Their unique properties allow for more effective and precise treatments while minimizing side effects.

What challenges exist in the clinical application of starvation therapy?

Challenges in the clinical application of starvation therapy include poor targeting, the potential for tumor adaptation and resistance, and the risk of adverse effects on healthy tissues. Overcoming these hurdles is critical for the successful implementation of starvation-based treatments.

What are the future directions for nanomaterials in cancer treatment?

Future directions include developing multifunctional nanoparticles that integrate various therapeutic strategies, responding to specific tumor microenvironments, and improving the efficacy of cancer treatments while reducing adverse effects.

References

1. World Health Organization. (2023). Cancer: Fact sheets. Retrieved from https://www.who.int/news-room/fact-sheets/detail/cancer
2. Tran, N. A., Moonshi, S. S., Lam, A. K., Lu, C. T., Vu, C. Q., & Arai, S. (2025). Nanomaterials in cancer starvation therapy: pioneering advances, therapeutic potential, and clinical challenges. Cancer Metastasis Reviews, 40(1), 167-169. https://doi.org/10.1007/s10555-025-10267-1
3. Tran, N. A. et al. (2025). Nanomaterials in cancer starvation therapy: pioneering advances, therapeutic potential, and clinical challenges. Cancer Metastasis Reviews, 40(1), 167-169. https://doi.org/10.1007/s10555-025-10267-1
4. Liu, Z., Chen, H. H., Zheng, L. L., Sun, L. P., & Shi, L. (2023). Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduction and Targeted Therapy, 8(1), 198. https://doi.org/10.1038/s41392-023-01460-1
5. Agrawal, S., Singh, G. K., & Tiwari, S. (2024). Focused starvation of tumor cells using glucose oxidase: A comprehensive review. International Journal of Biological Macromolecules, 281(Pt 3), 136444. https://doi.org/10.1016/j.ijbiomac.2024.136444
6. Yang, T., Zhang, X., Yang, X., Li, Y., Xiang, J., Xiang, C., et al. (2023). A mitochondria-targeting self-assembled carrier-free lonidamine nanodrug for redox-activated drug release to enhance cancer chemotherapy. Journal of Materials Chemistry B, 11(17), 3951–3957
7. Huang, Y., Gong, P., Liu, M., Peng, J., Zhang, R., Qi, C., et al. (2021). Near-infrared light enhanced starvation therapy to effectively promote cell apoptosis and inhibit migration. Materials Advances, 2(12), 3981–3992
8. Wang, Y. X., De Baere, T., Idee, J. M., & Ballet, S. (2015). Transcatheter embolization therapy in liver cancer: An update of clinical evidences. Chinese Journal of Cancer Research, 27(2), 96–121
9. Sidorenko, V., Scodeller, P., Uustare, A., Ogibalov, I., Tasa, A., Tshubrik, O., et al. (2024). Targeting vascular disrupting agent-treated tumor microenvironment with tissue-penetrating nanotherapy. Science and Reports, 14(1), 17513. https://doi.org/10.1038/s41598-024-64610-7
10. Muz, B., de la Puente, P., Azab, F., & Azab, A. K. (2015). The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl), 3, 83–92. https://doi.org/10.2147/HP.S93413