About this Research Topic
Although tumor heterogeneity has been well-known for its diverse roles in cancer progression, especially drug resistance and metastasis, the mechanisms underlying the development of tumor heterogeneity are largely unknown. Thus, it is critical to uncover mechanisms by which cancer cells used to generate heterogeneous cell populations and lead to intra-tumor heterogeneity. Cellular plasticity refers to the dynamic ability of cells to switch between distinct cellular status, such as epithelial-mesenchymal transition, stem cell to non-stem cell bidirectional conversions, has been proposed as an important cause of heterogeneity within a tumor. In addition, non-tumor cells in the tumor ecosystems, including fibroblasts or cancer-associated fibroblasts, immune cells, endothelial cells and pericytes, also contribute to intra-tumor heterogeneity and play important roles in tumor progression. However, the composition and spatial architecture of tumor cells and non-tumor cells in a tumor tissue are still elusive. High throughput Multi-omics sequencing techniques have been recently employed to classify molecular subtypes of diverse cancers and also elucidate the mechanisms of cancer initiation and progression, especially at single-cell levels, such as single-cell transcriptomics and genomic analyses.
In this research topic, we aim to further dissect the heterogeneity of tumor ecosystems using high-throughput multi-omics methods and human cancer specimens, including but not limited to single-cell RNA-seq, single-cell ATAC-seq and single-cell CNV-seq. Moreover, we will systematically identify regulators that control cellular plasticity and associated tumor heterogeneity and determine their contributions to drug resistance and metastasis of cancers. In addition, in order to identify targeted therapeutic strategies for cancer patients, we plan to model distinct subtype of cancers using multiple models (in vitro cellular models and in vivo mouse models), explore the underlying mechanisms and design personalized treatment strategies for each subtype.
For this Research Topic, we are interested in Original Research articles, Research briefs, Reviews, Mini Reviews, Methods, Perspectives and Commentaries that focus on the following topics:
• Use integrated omics (genomic, transcriptomic, proteomic, epigenetic, metabolic, etc.) to explore tumor heterogeneity and classify molecular subtypes of human cancers.
• Modeling distinct subtypes and investigating the underlying mechanisms of each subtype.
• Use single-cell analyses (scRNA-seq, scATAC-seq, scCNV-seq, CyTOF, etc.) to map the atlas of tumor ecosystems, including tumor cells, non-tumor cells and their interactions.
• Investigating the roles of non-tumor cells (tumor-infiltrating immune cells, cancer-associated fibroblasts, etc.) and their interaction with tumor cells in cancer initiation and progression.
• Investigating the roles and mechanisms of cellular plasticity (epithelial-mesenchymal transition, cell transdifferentiation and dedifferentiation, etc.) in drug resistance and metastasis.
• Development of small molecular drugs, antibodies, immune therapies or combinational therapeutic avenues that can manipulate cellular plasticity to kill cancer cells.
Keywords: Cancer, multi-omics analyses, cellular plasticity, tumor heterogeneity, targeted therapy
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