Aptamers as Theragnostic Tools in Prostate Cancer.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

Prostate specific membrane antigen (PSMA) expression in vena cava tumour thrombi of clear cell renal cell carcinoma suggests a role for PSMA-driven tumour neoangiogenesis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignant renal neoplasm with a peculiar propensity to propagate as a contiguous tumor extension via the renal vein and inferior vena cava, occasionally reaching the right atrium. This intravascular tumor extension, often referred to as a tumor thrombus, represents the active growing front of the cancer. Prostate specific membrane antigen (PSMA), a glycoprotein that is extensively used in prostate cancer diagnostics, is a useful vascular marker for a variety of solid tumors. It is expressed in renal carcinomas. The aim of the current investigation was to analyse and compare the expression of PSMA at the growing front of the vena cava tumor extension with that found in the primary renal lesion. METHODS: Immunohistochemical (IHC) analysis of PSMA and CD34 was performed on archived paraffin embedded vena cava tumour thrombus tissue and matching renal tumours. These specimens were collected from radical nephrectomies of 10 patients with vena cava invasive (pT3b) ccRCC in a large tertiary hospital in Australia. Quantitative and qualitative morphometric analysis of PSMA IHC expression was performed with Aperio ImageScope morphometry using intensity and positive pixel counts of CD34 and PSMA from the IVC tumour slides and the corresponding renal tumour mass. RESULTS: PSMA and CD34 immunostaining were noted in the neovasculature of IVC tumour and renal tumour tissue. There was a higher PSMA/CD34 positive pixel count ratio noted in IVC tumour tissue when compared to renal tumour tissue. PSMA showed consistently increased expression in vena cava tumour, in comparison with the renal tumour mass. CONCLUSIONS: Intravascular venous tumour extension expresses PSMA more intensely compared to intrarenal tumour tissue neovasculature. Our data suggest a possible mechanism for PSMA in neoangiogenesis and local progression of ccRCC and therefore its usefulness as a biomarker of neoangiogenesis for future diagnostic and therapeutic advancements.