Combination radionuclide therapy: A new paradigm

Targeted molecular radionuclide therapy (MRT) has shown its potential for the treatment of cancers of multiple origins. A combination therapy strategy employing two or more distinct therapeutic approaches in cancer management is aimed at circumventing tumor resistance by simultaneously targeting compensatory signaling pathways or bypassing survival selection mutations acquired in response to individual monotherapies. Combination radionuclide therapy (CRT) is a newer application of the concept, utilizing a combination of radiolabeled molecular targeting agents with chemotherapy and beam radiation therapy for enhanced therapeutic index. Encouraging results are reported with chemotherapeutic agents in combination with radiolabeled targeting molecules for cancer therapy. With increasing awareness of the various survival and stress response pathways activated after radionuclide therapy, different holistic combinations of MRT agents with radiosensitizers targeting such pathways have also been explored. MRT has also been studied in combination with beam radiotherapy modalities such as external beam radiation therapy and carbon ion radiation therapy to enhance the anti-tumor response. Nanotechnology aids in CRT by bringing together multiple monotherapies on a single nanostructure platform for treating cancers in a more precise or personalized way. CRT will be a key player in managing cancers if correctly tailored to the individual patient profile. The success of CRT lies in an in-depth understanding of the radiobiological principles and pathways activated in response.