Summary
Cancer is a disease of aberrant gene expression, and delineating the critical gene expression events during cancer development and progression is vital for cancer research. Here we summarize the role of novel RNA in situ hybridization technology in expanding the tool set available to researchers, thereby overcoming the challenges of cancer research in four key areas:
- Understanding tumor heterogeneity in gene expression
- Studying non-coding transcripts
- Developing biomarkers
- Driving and refining the diagnostic strategies of the future

Cancer is becoming an increasingly critical medical challenge, with the number of new cases expected to rise by about 70% globally over the next two decades.1 Since this disease essentially arises on the genomic level, investigating the tumor’s genomic and transcriptomic landscape is invaluable for both basic and translational cancer research.
Cutting-edge research employs a range of approaches to unravel the complexities of cancer, looking at the disease from all levels – the genome, the transcriptome, and the proteome. Over recent years, cancer transcriptomic profiling programs have proven that, like protein, RNA is a rich source of biomarkers for diagnosis, prognosis and predicting therapeutic response (recently coined as theranosis).2,3 Indeed, the significance of RNA within the cell has become increasingly apparent, with many discoveries indicating structural and regulatory functions. Alongside our growing understanding of RNA, methods for the analysis of this molecule are also evolving. The evolution of Next Generation Sequencing (NGS) technology over the past 10 years has offered cancer researchers the ability to look at the cancer genome and transcriptome, while PCR has offered researchers the ability to determine gene expression levels averaged across heterogeneous cell populations. However, up until now, a lack of robust methods for in situ analysis of RNA transcripts has held back the potential of RNA studies in cancer research. With the latest developments in RNA in situ hybridization (RNA ISH), however, this situation is changing.