RESUMEN
Liquid biopsies-tests that detect circulating tumor cellular components in the bloodstream-have the potential to transform cancer by reducing health inequities in screening, diagnostics, and monitoring. Today, liquid biopsies are being used to guide treatment choices for patients and monitor for cancer recurrence, and promising work in multi-cancer early detection is ongoing. However, without awareness of the barriers to adoption of this new technology and a willingness to build mitigation efforts into the implementation of widespread liquid biopsy testing, the communities that could most benefit may be the last to access and use them. In this work, we review the challenges likely to affect the accessibility of liquid biopsies in both the general population and underserved populations, and recommend specific actions to facilitate equitable access for all patients.
Asunto(s)
Células Neoplásicas Circulantes , Humanos , Biopsia LíquidaRESUMEN
Transcription factor (TF) proteins regulate gene activity by binding to regulatory regions, most importantly at gene promoters. Many genes have alternative promoters (APs) bound by distinct TFs. The role of differential TF activity at APs during tumour development is poorly understood. Here we show, using deep RNA sequencing in 274 biopsies of benign prostate tissue, localized prostate tumours and metastatic castration-resistant prostate cancer, that AP usage increases as tumours progress and APs are responsible for a disproportionate amount of tumour transcriptional activity. Expression of the androgen receptor (AR), the key driver of prostate tumour activity, is correlated with elevated AP usage. We identified AR, FOXA1 and MYC as potential drivers of AP activation. DNA methylation is a likely mechanism for AP activation during tumour progression and lineage plasticity. Our data suggest that prostate tumours activate APs to magnify the transcriptional impact of tumour drivers, including AR and MYC.