New Publication on Targeted Radionuclide Therapy

The molecular blueprint of targeted radionuclide therapy

A major review just published by members of Thera4Care in Nature Reviews Clinical Oncology outlines how a promising approach in oncology known as targeted radionuclide therapy (TRT) is rapidly evolving through a deeper understanding of molecular targets and their central role in achieving precise, personalised treatment across a wide range of cancers.

The paper is authored by Irina Primac, Kevin Tabury and Sarah Baatout of the Belgian Nuclear Research Centre (SCK CEN), together with Alpaslan Tasdogan and Ken Herrmann of the University Hospital Essen.

In simple terms, TRT works by combining two powerful ideas: molecular targeting, identifying biological markers or “flags” on tumour cells, and radiation therapy, in which a therapeutic radionuclide is attached to a ligand that recognises these markers. The Review shows how researchers are designing radiopharmaceuticals that deliver their radioactive payload specifically to molecular targets, ensuring that radiation acts where it is needed, on cancer cells, while limiting exposure to healthy tissues.

Why this matters

Conventional cancer treatments such as chemotherapy and external beam radiation lack molecular selectivity and often damage healthy tissues alongside tumour cells, leading to significant side-effects. TRT, by contrast, is built on target recognition, enabling more refined delivery of therapeutic radiation and offering the potential for better tolerance and improved patient quality of life. The Review highlights the “transformative potential” of selecting optimal molecular targets to increase precision and therapeutic impact.

Cancer is highly heterogeneous. Even within the same cancer type, patients may express different molecular targets. Tailoring treatment based on these profiles is therefore crucial both medically and socially. It may reduce ineffective treatments, limit toxicities and ultimately lower healthcare costs. The Review envisions TRT becoming a “highly individualised and adaptable” treatment modality in oncology.

What the Review covers

The Review provides a broad survey of the molecular target landscape of TRT. It summarises established targets already used clinically, targets currently advancing through the clinical development pipeline and emerging targets identified through molecular profiling and deep characterisation of tumour biology. Importantly, the Review emphasises both pan-cancer and cancer-specific targets, including those within the tumour microenvironment that can be exploited for selective radiation delivery.

Challenges and opportunities

A central theme of the Review is the challenge of selecting the right target for the right patient and cancer type. The authors highlight the importance of ensuring that radiopharmaceuticals reach the tumour in sufficient quantity, of avoiding uptake in healthy tissues that may express related markers and of navigating tumour heterogeneity and dynamic changes in target expression. These factors determine whether a molecular target is suitable for safe and effective TRT.

Future directions

The Review explores how TRT may expand through the identification of new molecular targets and through strategies that increase therapeutic efficacy. These include integrating TRT earlier in treatment pathways, combining TRT with immunotherapies or chemotherapies and using advanced imaging and molecular diagnostics to guide target selection and optimise therapy for each patient.

Social impact — big picture

More precise targeting may reduce side-effects, shorten hospital stays and extend effective treatment options to cancers with limited current therapies. Broadening the range of viable molecular targets also expands the potential reach of this therapeutic modality.

However, the Review notes that despite rapid progress, TRT is currently used mainly in a few cancers such as neuroendocrine tumours and prostate cancer. Developing radiopharmaceuticals against additional targets will broaden access, and several initiatives are described across both well-known and rare cancers. From a healthcare systems perspective, effective TRT has the potential to reduce repeated treatments and hospital admissions, although initial investment is essential.

What’s next

Although highly promising, TRT is not yet widely implemented across all cancer types. The Review emphasises the need for clinical trials that better reflect real-world tumour complexity, for improved tools that support target discovery and validation and for dynamic monitoring systems that match patients with the most suitable molecular target.

The message is hopeful with a future of more effective, personalised and less harmful cancer treatment is steadily approaching. Achieving this vision will require sustained investment in scientific research and in healthcare systems capable of delivering TRT safely and equitably.

Click here to read the full Review:https://www.nature.com/articles/s41571-025-01069-z