Extracellular vesicle biomarkers redefine prostate cancer radiotherapy
Hei Yeung Chan, Qi Wang, Andrew Howie, Joseph Bucci, Peter Graham, Yong Li
Abstract
Radiotherapy (RT) remains a cornerstone in the treatment of prostate cancer (PCa). Extracellular vesicles (EVs), nano-sized particles secreted by cells, play important roles in intercellular communication within the tumour microenvironment (TME) and contribute to tumour growth, metastasis, and therapy resistance. Recent advancements demonstrate the potential of EVs as biomarkers for cancer diagnosis, prognosis, and treatment monitoring. Accumulating evidence supports the role of EVs in modulating RT outcomes by shaping the TME, mediating radioresistance, and influencing cancer metastasis. Despite substantial progress, challenges remain, including the heterogeneity of EV biogenesis, variability in cargo composition, and the absence of standardised methods for EV isolation and characterisation. While the therapeutic and diagnostic prospects of EVs in PCa management are promising, further research is needed to clarify the mechanisms through which EVs impact RT and to translate these findings into clinical practice. Incorporating EV research into PCa treatment paradigms could enhance diagnostic accuracy, enable real-time monitoring of RT responses, and support the development of new targeted therapeutic strategies. This review discusses recent progress in understanding EVs in the context of RT for PCa, focuses on their roles in modulating tumour growth, contributing to radioresistance within the TME, and facilitating the monitoring of RT efficacy and recurrence. In addition, the potential of EVs as biomarkers for liquid biopsy and their applications in enhancing radiosensitivity or overcoming radioresistance is also explored. • Challenges remain in using biomarkers to track PCa progression and assess RT treatment effects. • EVs modulate the tumour microenvironment and offer a promising source for liquid biopsy and PCa RT monitoring. • EV-derived biomarkers show potential for assessing RT efficacy and predicting PCa recurrence. • Radiation-induced EVs contribute to radioresistance and may serve as targets to enhance PCa radiosensitivity. • Developing better in vitro and in vivo models will improve PCa RT and support clinical translation,