Clinical OMICS

MAY-JUN 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 25 of 47

24 Clinical OMICs May/June 2017 within the tumor, or within a cancer, will be of real impor- tance to design better anticancer treatments in the future." Dr. Courtois believes her recent findings in colorectal can- cer could lead to direct patient benefits. "Single cell transcrip- tomics can allow us to identify new biomarkers that we can use for future clinical use," she said. "For example, we iden- tified different types of fibroblasts in our study and we have specific markers for each type. Maybe in the future we can develop a panel that can screen for both different types of fibroblasts present in the tumor and have a prognostic effect." Dr. Tirosh and his colleagues recently discovered that gli- omas with a mutation in the IDH1 or IDH2 genes are made up of three different populations of cancer cells. Two of these types do not proliferate, but the third population of cells was linked to tumor growth and aggressiveness. "This latter subpopulation, which is consistent with the cancer stem cell model, is the least frequent and was never previously described, but it is the one that we need to target in order to eradicate glioma," he emphasized. "In future work, we will study the regulation of this sub- population with the goal of developing new treatments that directly target those glioma stem cells. Another future direc- tion involves longitudinal studies in which we would … fol- low the evolution of the tumor over time and how it changes following treatments and development of drug resistance." While single-cell genomics and transcriptomics have advanced enormously in the last 5 years, both techniques still require refinement. Dr. Hacohen cautioned: "I think that it will take a while, like all things when a new technology develops, for the discoveries to become robust enough that you can say this is going to be what we do for this patient." In order to successfully sequence RNA from a single cell, researchers must convert it into a copy DNA library that can then be sequenced. Dr. Hacohen explained that the efficiency of such conversion is still very low at around 5% to 10%. He added that the problem is even worse for DNA as, while there are multiple copies of RNAs in a single cell, there are only two copies of the DNA. "Via the transcriptome, at least there are multiple copies of the RNA so if there are 10 copies of the RNA maybe you'll see one or if there are a 100 copies you'll see 10 of them. That's pretty good, but with DNA if your efficiency is low you are simply not going to see certain events. So I think sensitivity is probably the biggest issue right now, I would say. The sensitivity is not high enough." Future Directions Single-cell cancer genomics has developed rapidly over the last five years and is likely to continue to do so over the next decade. Based on recent research, it seems likely that it will continue to expand our understanding of tumor het- erogeneity and allow rare, potentially disease-causing or resistance-associated subpopulations of cells to be identi- fied more easily. This improved understanding of the cell biology of tumors will also lead to better design of targeted cancer drugs and provide insight into the mechanisms of drug response to current therapies. If the current upwards trajectory of technology develop- ment continues, such techniques will become more accurate, efficient and affordable. "I believe we will arrive at higher accuracy DNA and RNA sequencing together with method- ologies where we are able to do this on the same single cell," predicted Dr. Voet. Additional ways in which single-cell techniques are fore- cast to develop include the ability to image genes and their activity during analysis. "Imagine taking a section of the tumor and imaging thou- sands of genes and their activity in every cell. So you can see not only what state are the cells in, but also where they are," commented Dr. Hacohen. "Are they next to the tumor? Are they far away from the tumor? Are two cell types that interact next to each other or far away from each other? These are things that we hav- en't been able to do very well by the current methods where we dissociate the cells and study them individually, and so I think it's going to be important to link spatial analysis under single-cell technologies." Dr. Voet agrees. "These technologies will be brought to a spatial context so that we can interrogate tissue slices from a single cell perspective and we can learn about the gene expression profiles in a spatial context." While improvements in amplification efficiency and sensi- tivity are still needed to help the techniques reach the clinic, it seems certain that single-cell cancer genomics is here to stay. "There is really a technological movement right now that is unprecedented in biology," emphasized Dr. Hacohen. "It will bring us to a deeper understanding of cancer that will both lead to greater discovery and therapeutic targets, but also indirectly affect patient care as well." (continued from page 22) "Single-cell transcriptomics can allow us to identify new biomarkers that we can use for future clinical use." —Elise Courtois, Ph.D.

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