Abstract
Cancer ranks among the top triumvirate leading causes of human deaths worldwide. The pathological mechanisms are notably intricate, demonstrating proliferative and metastatic capabilities, which complicate therapeutic interventions. The sigma-1 receptor (σ(1)R) plays a crucial role in tumor survival and migration, while the sigma-2 receptor (σ(2)R) is intimately associated with tumor proliferation. This review encapsulated the investigation concerning σ(1)R and σ(2)R in neoplasms and rigorously summarized the ligands and radio-ligands development and their tumor applications, such as antitumor cell proliferation and PET/SPECT imaging in tumors. A comprehensive classification discussion was undertaken regarding the chemical structures and emphasized the possibility of dual/multitargeted ligands. Ultimately, we discussed the effects of chiral structures and the pharmacological characteristics of ligands on affinity and pharmacokinetic features in vivo, particularly concerning radiopharmaceuticals. This review functions as a beneficial resource, fostering ligand deployment and stimulating the generation of innovative ideas for developing innovative radiopharmaceuticals.