January 19 2022
The Heterogeneity of Tumors
One of the greatest challenges for anticancer therapies is the heterogeneity within cancerous tumors. Within a single tumor, there are often multiple subpopulations of cells with different genetic mutations, transcriptional programs and microenvironments that alter the tumor’s response to treatments.
To better characterize the cumulative effects of different transcriptional programs between cells in the same tumor, researchers from Genentech developed a new single-cell RNA sequencing (scRNA-seq)-a based platform called TraCe-seq.
What is TraCe-Seq?
Published in Nature Biotechnology in September 2021, TraCe-seq (short for tracking differential clonal response by scRNA-seq) is able to identify the origin, fate, and transcriptional programs of distinct cell populations in response to different treatments.
This technique uses clonal fitness mapping, or the measurement of the survival of different populations of ‘clones’ or identical cells, combined with an expressed ‘barcode’ for identification of different clonal populations.
The resulting workflow and data analysis allows for single-cell resolution measurements of gene expression in response to different treatments, which can illustrate the distinct transcriptional features of a heterogenous tumor and how those features affect drug response or resistance.
Applying TraCe-Seq to Cancer Research
The authors applied TraCe-seq to compare the efficacy and mechanisms of action of new EGFR inhibitor-degraders to EGFR kinase inhibitors in lung cancer cells with mutant EGFR. They found that EGFR degradation was less effective at inhibiting growth than the traditional EGFR kinase inhibitors and that an endoplasmic reticulum (ER) protein processing pathway is upregulated and essential to effective anti-EGFR therapy.
The Future of scRNA-seq Analysis
These results highlight the utility of a technique like TraCe-seq, where the high resolution of scRNA-seq can be leveraged to uncover new aspects of transcriptional biology. Continuous innovation in the development of sequence analysis pipelines will lead to more research breakthroughs, and in the case of cancer research, far more effective treatments.
Jane Cook, Journalist & Content Writer, Bridge Informatics
Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in the management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email [email protected] or [email protected].