Transforming Cancer Treatment: The Evolving Landscape of Targeted α-Particle Therapy

Abstract

Targeted α-particle therapy, a promising innovation in the field of cancer treatment, represents a convergence of groundbreaking science, advanced technology and the potential to revolutionise oncology. This review explores the historical development, mechanisms of action, preclinical and clinical applications, safety considerations and the future directions of targeted α-therapy. We delve into the evolution of this therapy from the early experiments with alpha particles to the synthesis of α-particle-emitting radionuclides, highlighting the key milestones that paved the way for its clinical translation. The mechanisms of action section elucidates the radiobiology of α-particles, focusing on their high linear energy transfer and deoxyribonucleic acid-damaging properties. In addition, we discuss the immunomodulatory effects of α-therapy, offering insights into its broader impact on the immune system’s response to cancer. Preclinical studies, informed by animal models and in vitro experiments, provide essential information on the efficacy and toxicity profiles of α-therapy. Lessons from these studies guide the transition from laboratory success to clinical trials, which are comprehensively reviewed, offering a glimpse into ongoing and completed studies as well as their associated challenges and limitations. Patient selection, diagnostic imaging, and safety considerations are paramount in the clinical translation of targeted α-therapy. We explore personalised treatment approaches, dosimetry calculations and advancements in imaging techniques that aid in treatment planning. Moreover, we discuss future directions, including the potential for combination therapies and non-oncological applications of α-therapy. Finally, regulatory and economic aspects are addressed, recognising the importance of approvals from agencies such as the Food and Drug Administration and international regulatory bodies. Considerations of market dynamics, cost-effectiveness and patient access are crucial in assessing the feasibility and integration of α-therapy into mainstream oncology. In conclusion, targeted α-particle therapy emerges as an evolution in cancer treatment, with the potential to redefine the oncology landscape. To unlock its full potential, multidisciplinary collaboration, ongoing research and dedicated efforts to address safety and regulatory aspects are imperative. This review encapsulates the journey toward establishing targeted α-therapy as a standard of care and sets the stage for the next chapter in the fight against cancer.