The Future of Oncology is Hybrid

Why combination therapy with TRT is gaining momentum

Despite remarkable progress in oncology, many cancers remain difficult to treat once they relapse or resist first-line therapy. The standard of care—chemotherapy, targeted agents, or immunotherapy—has extended survival for millions of patients, yet resistance and toxicity still limit long-term benefits. The question today is not whether we can treat cancer, but how can we treat it better.

Among the therapeutic innovations reshaping this landscape, Targeted Radiotherapy (TRT) stands out as a modality that brings precision and power together. By using radiopharmaceuticals that deliver radioactivity to cancer cells, TRT attacks tumors from within, minimizing collateral damage to surrounding healthy tissue. Its targeted nature makes it a natural complement to established treatments — and combining the two could open a new chapter in cancer care.

Cancer is a multifactorial disease, driven by genetic instability, molecular signaling, and immune escape. No single therapy can address all these mechanisms. That’s why combining TRT with existing therapies has become such an appealing strategy. Targeted radiation does more than destroy tumor cells: it alters the tumor microenvironment, as well as immune response, and can increase the effectiveness of drugs that rely on the same or complementary biological effects.

Some of the most promising approaches, but not limited to, involve pairing TRT with immunotherapy or with DNA repair inhibitors. When combined with immunotherapy, TRT (also known as Radioimmunotherapy, RIT) can make tumors more visible to the immune system, triggering a broader and more aggressive anti-tumor response. When combined with agents such as PARP inhibitors, it amplifies DNA damage beyond what either therapy could achieve alone, delivering a synergistic therapeutic effect. Early studies suggest these combinations can lead to stronger, more durable responses — not by replacing the standard of care, but by reinforcing it.

From concept to clinic: designing meaningful combinations with TRT

Designing such combination therapies, however, requires careful balance. Each therapy brings its own pharmacological and safety profile, and synergy must not come at the cost of added toxicity. Preclinical studies therefore play a central role, starting with small-scale tolerance and toxicity assessments to define safe dosing ranges before progressing to efficacy studies that test different treatment dosing and schedule combinations. Translational research and integrated expertise are key to this process, ensuring that the biological behaviors of each compound are fully understood before moving into clinical development.

In practice, the momentum behind combinations with TRT follows several distinct development paths, reflecting where both the standard-of-care drug and the radiopharmaceutical sit on the clinical maturity curve. Therapies such as Lutathera® illustrate how molecularly targeted radiation has moved beyond innovation into routine clinical use, making these combinations a logical and relatively de-risked next step.

In the most established scenario, a standard-of-care drug in its conventional form is combined with its TRT counterpart, which has itself reached standard-of-care status. In this case, both components are already clinically validated, and the combination builds on well-characterized safety and efficacy profiles. This is typically the case when an immunotherapy is paired with its radio-immunotherapy counterpart, using the same targeting antibody to deliver both biological and radiological activity against the tumor.

A second, increasingly common scenario involves a new oncological candidate that has progressed to Phase II clinical development, combined with a validated standard-of-care TRT. Here, developers seek to enhance or differentiate their emerging therapy by pairing it with a proven radiopharmaceutical. This approach allows companies to explore synergistic benefit while anchoring their program to an established treatment backbone, helping to control uncertainty during clinical expansion.

The third scenario turns the equation around: a well-established standard-of-care drug is combined with a novel TRT candidate. In this case, the standard-of-care therapy serves as a reference framework against which the new radiopharmaceutical can be evaluated. By integrating TRT into an existing treatment paradigm, developers can more clearly demonstrate added value, mechanism-driven benefit, and clinical relevance.

Together, the above approaches highlight an important shift in oncology development. Combination strategies are no longer exploratory experiments, but structured pathways designed to accelerate translation while managing risk. As radiopharmaceuticals increasingly join the ranks of standard treatments, they are becoming integral building blocks in the design of next-generation, multimodal cancer therapies.

Yet developing these combinations is not without challenges. Radiopharmaceuticals involve complex logistics — radioisotope production, radiolabeling, regulatory constraints — areas that are often unfamiliar to conventional drug developers. This is why collaboration between biopharma companies and specialized CROs and CDMOs is becoming essential. The ability to combine pharmacology, radiochemistry, nuclear imaging and bioanalysis expertise within one program is what transforms a scientific concept into a clinically viable reality.

The next generation of cancer therapy will not be defined by a single molecule or modality. It will be shaped by intelligently designed combinations — treatments that harness the strengths of each component to achieve more than the sum of their parts. The meeting point between TRT and the standard of care is more than a technical milestone; it represents a conceptual shift in how we approach oncology. It’s a move from isolated mechanisms to integrated solutions, from treating disease to truly understanding it. And in that convergence lies one of the most promising paths forward for patients and for the future of precision medicine.

As combination strategies involving targeted radiotherapy continue to mature, their success will depend on thoughtful design, robust preclinical validation, and seamless translation across disciplines. Advancing these programs requires more than adding modalities together, it demands an integrated understanding of pharmacology, radiochemistry, imaging and tumor biology. For teams exploring how TRT can reinforce existing standards of care, early, data-driven decisions in preclinical development can be decisive. Engaging with partners who combine expertise across these domains helps turn promising concepts into clinically meaningful combination therapies.