Combination Therapy, a Promising Approach to Enhance the Efficacy of Radionuclide and Targeted Radionuclide Therapy of Prostate and Breast Cancer.

Simone U. Dalm,Tyrillshall S. T. Damiana

doi:10.3390/pharmaceutics13050674

Abstract

In recent years, radionuclide therapy (RT) and targeted radionuclide therapy (TRT) have gained great interest in cancer treatment. This is due to promising results obtained in both preclinical and clinical studies. However, a complete response is achieved in only a small percentage of patients that receive RT or TRT. As a consequence, there have been several strategies to improve RT and TRT outcomes including the combination of these treatments with other well-established anti-cancer therapies, for example, chemotherapy. Combinations of RT and TRT with other therapies with distinct mechanisms of action represent a promising strategy. As for prostate cancer and breast cancer, the two most prevalent cancer types worldwide, several combination-based therapies have been evaluated. In this review, we will provide an overview of the RT and TRT agents currently used or being investigated in combination with hormone therapy, chemotherapy, immunotherapy, and external beam radiation therapy for the treatment of prostate cancer and breast cancer.

Highlights

Radionuclide therapy (RT) involves the use of radionuclides that target specific cellular processes or accumulate in cancer cells because of their chemical properties [1]
Even though the prostate-specific membrane antigen (PSMA) radiotracer was used for imaging purposes in this study, these findings indicate the high potential of combination therapy when a PSMA radiotracer coupled to a therapeutic radionuclide is applied
The rising interest in targeted radionuclide therapy (TRT) has led to the evaluation of several combination strategies

Summary

Introduction

Radionuclide therapy (RT) involves the use of radionuclides that target specific cellular processes or accumulate in cancer cells because of their chemical properties [1]. Targeted radionuclide therapy (TRT) uses radiotracers that target molecules that are overexpressed on cancer cells. In the treatment of large tumors, for example, β− -emitters are considered the ideal radionuclide These β− -emitters have a long track length and neighboring tumor cells that lack expression of the targeted molecules are exposed to radiation, the so-called “cross-fire” effect [6,7]. The broad option of targeting agents, together with the wide range of radionuclides with unique properties, allows radiotracers to be designed for targeting different types of cancers at different disease stages. Besides having the most optimal radiopharmaceutical, for the treatment to be effective, several other factors should be considered, including the cumulative radiation dose delivered, tissue and dose penetration, and the density of the targeted molecule on cancer cells. This review will provide an overview of RT and TRT agents currently used or being investigated in combination with hormone therapy, chemotherapy, immunotherapy, and local external beam radiation therapy (EBRT) for the treatment of prostate cancer (PCa) and breast cancer (BC)

Prostate and Breast Cancer

Hormone Therapy-Based Combination Therapy

Chemotherapy-Based Combination Therapy

Immunotherapy-Based Combination Therapy

External Beam Radiation Therapy-Based Combination Therapy

Findings

Discussion and Conclusions