Single Cell Sequencing: A New Dimension in Cancer Diagnosis and Treatment
Cancer is one of the leading causes of death worldwide and well known for its complexity. Cancer cells within the same tumor or from different tumors are highly heterogeneous. Furthermore, stromal and immune cells within tumor microenvironment interact wi
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Single Cell Sequencing: A New Dimension in Cancer Diagnosis and Treatment Fengying Wu, Jue Fan, Jingwen Fang, Priya S. Dalvi, Margarete Odenthal, and Nan Fang
Abstract
Cancer is one of the leading causes of death worldwide and well known for its complexity. Cancer cells within the same tumor or from different tumors are highly heterogeneous. Furthermore, stromal and immune cells within tumor microenvironment interact with cancer cells to play important roles in how tumors progress and respond to different treatments. Recent advances in single cell technologies, especially massively parallel single cell sequencing, have made it possible to analyze cancer cells and cells in its tumor microenvironment in parallel with unprecedented high resolution. In this chapter, we will review Fengying Wu and Jue Fan contributed equally to this work. F. Wu Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China J. Fan · J. Fang Singleron Biotechnologies, Nanjing, Jiangsu, China P. S. Dalvi · M. Odenthal Institute for Pathology, University Hospital of Cologne, Cologne, Germany Centre for Molecular Medicine Cologne, University of Cologne (UoC), Cologne, Germany N. Fang (*) Singleron Biotechnologies, Nanjing, Jiangsu, China Department of Pathology, Anhui Medical University, Hefei, Anhui, China e-mail: [email protected]
recent developments in single cell sequencing technologies and their applications in cancer research. We will also explain how insights generated from single cell sequencing can be used to develop novel diagnostic and therapeutic approaches to conquer cancer. Keywords
Single cell sequencing · Tumor microenvironment · Diagnosis · Therapy
9.1
Background
Cancer is one of the leading causes of death in the world, accounting for 18.1 million new cases and 9.6 million deaths in 2018 [1]. Over the last decades, the treatment of malignant tumors has undergone rapid improvements with the use of targeted therapy and immunotherapy and the overall survival rate of cancer patients has increased significantly. For example, the 5-year survival rate of advanced lung cancer patients increased from 3% to current 16% after use of anti-PD1/PD-L1 immunotherapy [2]. However, big challenges remain. For targeted therapy, there are patients with actionable mutations who cannot benefit from tyrosine kinase inhibitors (TKIs), while the underlining mechanism for such primary resistance is still unclear. Besides primary resistance, almost all patients will eventually develop resistance to the TKIs. For
# Springer Nature Singapore Pte Ltd. 2020 B. Yu et al. (eds.), Single-cell Sequencing and Methylation, Advances in Experimental Medicine and Biology 1255, https://doi.org/10.1007/978-981-15-4494-1_9
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example, non-small cell lung cancer (NSCLC) patients with EGFR mutations who are treated with EGFR-TKIs often develop resistance by gain of additional mutations in the EGFR locus, such as the common gatekeeper T790M mutation (50–60%) [3] or mutations at EGFR codons D761 [4], L747 [5], or C797 [6].
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