Targeted Radiation and Immune Therapies—Advances and Opportunities for the Treatment of Prostate Cancer

Abstract

Prostate cancer is the most diagnosed malignancy in men in the United States and the second leading cause of cancer-related death. For localized disease, radiation therapy is a standard treatment that is often curative. For metastatic disease, radiation therapy has been primarily used for palliation, however, several newer systemic radiation therapies have been demonstrated to significantly improve patient outcomes and improve survival. In particular, several targeted radionuclide therapies have been approved for the treatment of advanced-stage cancer, including strontium-89, samarium-153, and radium-223 for bone-metastatic disease, and lutetium-177-labeled PSMA-617 for patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castration-resistant prostate cancer (mCRPC). Contrarily, immune-based treatments have generally demonstrated little activity in advanced prostate cancer, with the exception of the autologous cellular vaccine, sipuleucel-T. This has been attributed to the presence of an immune-suppressive prostate cancer microenvironment. The ability of radiation therapy to not only eradicate tumor cells but also potentially other immune-regulatory cells within the tumor immune microenvironment suggests that targeted radionuclide therapies may be well poised to combine with immune-targeted therapies to eliminate prostate cancer metastases more effectively. This review provides an overview of the recent advances of targeted radiation agents currently approved for prostate cancer, and those being investigated in combination with immunotherapy, and discusses the challenges as well as the opportunities in this field.

Research progress on deep learning in magnetic resonance imaging–based diagnosis and treatment of prostate cancer: a review on the current status and perspectives

“…Radiotherapy is an indispensable treatment modality for cancer patients, either as neoadjuvant or postoperative therapy, in combination with chemotherapy ( 119 , 120 ). The main goal of radiotherapy is to maximize the therapeutic gain ratio by delivering an effective radiation dose to the planned target volume (PTV) and avoiding unnecessary radiation exposure to adjacent healthy tissues and organs at risk (OARs) ( 121 , 122 ). However, manual segmentation of the prostate gland, which is necessary for accurate mapping of PTV and OARs, is prone to errors and can result in less accurate and sensitive outcomes than those desired clinically.…”

Unleashing novel horizons in advanced prostate cancer treatment: investigating the potential of prostate specific membrane antigen-targeted nanomedicine-based combination therapy

“…For patients with suspicious PCa or at risk for PCa, MRI has already been involved as the preferable imaging tool due to its promising spatial and soft tissue resolution ( 88 – 90 ). While in terms of PCa therapy, the accurate delineation of planned target volume (PTV) and organs at risk (ORA) based on the medical images acquired is a fundamental prerequisite for the successful delivery and positive outcomes of radiotherapy ( 91 – 93 ). The conventional contrast agents used in MRI are transition metallic elements and paramagnetic lanthanide-containing cations such as gadolinium (III) (Gd 3+ ) and manganese (II) (Mn 2+ ) ( 94 , 95 ) agents.…”

“…This synergistic approach amplifies the responsiveness of tumor cells to radiation by augmenting the effective dosage delivered to these cells while minimizing impact on normal tissues. This is achieved through the acceleration of DNA damage, ultimately heightening the anti-tumor effect ( 92 , 93 , 143 , 144 ). Among high atomic number (Z) metallic NMLs, gold NP (Z=79) has been well-studied based on its physicochemical properties and its induced cellular biological actions ( 145 – 147 ) ( Figure 3 ).…”

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

“…Patients with mCRPC with disease progression after treatment with enzalutamide or abiraterone could be treated with Olaparib, which has demonstrated longer progression-free survival [ 19 ]. Other novel treatment options include the PSMA-targeted radio ligand therapy (RLT), immunotherapy, or cell-based immunotherapy, but these approaches still have limited success and are currently being tested [ 16 , 20 ].…”