RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis

Abstract

Prostate cancer is the third leading cause of male cancer deaths in the developed world. The current lack of highly specific detection methods and efficient therapeutic agents for advanced disease have been identified as problems requiring further research. The integrins play a vital role in the cross-talk between the cell and extracellular matrix, enhancing the growth, migration, invasion and metastasis of cancer cells. Progression and metastasis of prostate adenocarcinoma is strongly associated with changes in integrin expression, notably abnormal expression and activation of the β3 integrins in tumour cells, which promotes haematogenous spread and tumour growth in bone. As such, influencing integrin cell expression and function using targeted therapeutics represents a potential treatment for bone metastasis, the most common and debilitating complication of advanced prostate cancer. In this review, we highlight the multiple ways in which RGD-binding integrins contribute to prostate cancer progression and metastasis, and identify the rationale for development of multi-integrin antagonists targeting the RGD-binding subfamily as molecularly targeted agents for its treatment.

Recent progress in development of siRNA delivery vehicles for cancer therapy

“…Arginine-glycine-aspartic acid (RGD) peptide and folate are typical ligands used in siRNA delivery for various types of cancers because these ligands are closely related to angiogenesis of tumor development and metabolism of fast-growing cancer cells. The RGD peptide can strongly and specifically bind to α v β 3 and α v β 5 integrin receptors, which are overexpressed on many cancerous and neovascular endothelial cell surfaces [82,83]. A cyclic form of the RGD peptide (cRGD) provides the rigid structure for enhanced affinity to the target integrins (K D = approximately 40 nM for α v β 3 integrin [84]) and prevents degradation of the highly susceptible aspartic acid residue [82].…”

RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer

“…Thus, we hypothesize that therapeutic agents targeting αvβ3 integrin would be particularly promising for the treatment of bone metastases with improved therapeutic efficacy by targeting tumor cells and by inhibiting integrin-involved bone metastases. To date, there is preclinical evidence that RGD peptides as αvβ3 integrin antagonist can successfully block osteoclast-mediated osteolysis in animal models of bone metastases and some of them have advanced to clinic [21,23]. On the other hand, RGD peptides conjugated drug delivery system targeting αvβ3 integrin for targeted tumor theragnostics has been also well documented in animal models of primary tumors [24,25].…”

A heterodimeric [RGD-Glu-[64Cu-NO2A]-6-Ahx-RM2] αvβ3/GRPr-targeting antagonist radiotracer for PET imaging of prostate tumors

“…Identification of prostate tumors at an early stage continues to be challenging for oncologists and is of great clinical importance [2, 3]. Although direct mortality from non-metastatic prostate cancer is relatively low, the grave prognosis, excruciating pain, and increasing costs of palliative therapy associated with the chronic and metastatic stages of the disease drives continued and intensified investigations toward the development of novel and more effective means of earlier, accurate detection and therapy.…”