Expansion to hard-to-treat tumours

With proof-of-concept established in GEP-NETs and mCRPC, radiopharmaceutical development has expanded to target over 15 malignancies across solid and haematologic tumours. Innovations are focusing on novel targets not yet fully explored by other treatment modalities, such as hexokinase 2 (HK2), neurotensin receptor 1 (NTSR1), and gastrin-releasing peptide receptor 1 (GRPR1).

Improving adverse event profiles

Next-generation targeted radiotherapeutics aim to enhance radioisotope targeting to improve efficacy and reduce toxicity. Innovations include:

• Radio DARPin constructs: These genetically engineered antibody mimetic proteins offer high specificity and affinity for target proteins, potentially reducing uptake by healthy tissues and organs, such as the kidneys.
• Tumour microenvironment (TME) exploitation: Constructs that exploit unique features of the TME, such as lower pH, greater hypoxia, or specific enzymatic activity, to activate or enhance ligand/small molecule or monoclonal antibody (mAb)-mediated binding.
• Single domain antibodies and nanobodies: These exhibit shorter blood half-lives, enhanced tumour uptake, and superior binding affinity and specificity for target biomarkers.

The potential for synergistic effects drives the transition from monotherapy to combination therapy. Rationally designed combination therapies include:

• DNA repair inhibitors: Such as PARP inhibitors, which enhance the efficacy of radiotherapy.
• Immune checkpoint inhibitors: Anti-PD-(L)1 agents that leverage radiotherapy-induced neo-antigens to boost immune response.
• Chemotherapeutics: Established radiosensitisers in chemoradiation protocols that enhance the effects of radiotherapy.

Strategic acquisitions and partnerships among major pharmaceutical companies, such as those by Novartis, Bayer, Eli Lilly, and Bristol Myers Squibb, highlight the intense interest and investment in this field. These collaborations are not only expanding the range of available treatments but also driving innovation in targeting mechanisms and combination therapies. By addressing challenges unique to radiopharmaceuticals, including supply chain logistics, manufacturing, distribution, and prescriber education, the industry is paving the way for more widespread adoption and integration into standard oncology care.

Looking forward, the integration of next-generation targeted radiotherapeutics into combination regimens promises to enhance efficacy and expand their use across various stages of cancer treatment. Innovations such as alpha-emitting radioisotopes and novel targeting constructs are expected to further improve clinical outcomes, reduce adverse events, and provide new avenues for treating a broader range of malignancies.

As the clinical evidence continues to validate the efficacy and safety of these therapies, targeted radiopharmaceuticals are poised to become a cornerstone of modern oncology. The ongoing development and strategic investments in this field reflect a commitment to improving patient outcomes and addressing unmet needs in cancer care. The future of oncology is bright, with targeted radiopharmaceuticals leading the charge toward more personalised, more effective, and less invasive cancer treatments.

The emerging era of targeted radiopharmaceuticals represents a paradigm shift in the treatment of cancer. Through continued innovation, strategic partnerships, and a focus on addressing key challenges, these therapies have the potential to become a central pillar in the fight against cancer.