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Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
Spatial biology of crowded tumor cells: A new map for designing drug combinations
1Biophysics and Computational Biology Section, Frederick National Laboratory for Cancer Research in the Cancer Innovation Laboratory, National Cancer Institute, Frederick, MD, 21702, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Abstract:
Understanding how tumor cells navigate crowded spatial environments to drive progression and how to deter them is challenging. Intracellularly, dynamic protein ensembles link genotype to phenotype. Dysregulation of these ensembles-driven by overexpression and mutational variants-alters the conformational landscapes, shifts cell states, and reshapes cell fate decisions. This diversity, spanning from the molecular level to the tumor microenvironment, triggers resistance mechanisms precipitating efforts to engineer effective combination strategies. Here, we underscore these transient cell states in migration and tissue adaptation, which depend on transcriptomic and signaling compatibility. Our spatial biology outlook envisions a map for designing drug combination strategies targeting both the primary tumor and disseminating cell states with host tissue commonalities, centering on bypass pathways to deter drug resistance and metastasis.
Insights
Tumor cells
Area of Science:
- Cancer Biology
- Molecular Oncology
- Spatial Biology
Background:
- Tumor cell navigation in crowded environments drives progression and resistance.
- Intracellular protein ensembles link genotype to phenotype, with dysregulation altering cell states and fate.
- Tumor microenvironment diversity triggers resistance, necessitating combination strategies.
Purpose of the Study:
- To understand tumor cell navigation and develop strategies to deter them.
- To underscore transient cell states in migration and tissue adaptation.
- To map drug combination strategies targeting primary and disseminating tumor cells.
Main Methods:
- Spatial biology approaches.
- Analysis of transcriptomic and signaling compatibility.
- Focus on bypass pathways to overcome drug resistance.
Main Results:
- Transient cell states are crucial for tumor cell migration and tissue adaptation.
- Transcriptomic and signaling compatibility influence these cell states.
- Spatial biology offers a framework for combination therapy design.
Conclusions:
- Targeting transient cell states and bypass pathways is key to deterring drug resistance and metastasis.
- A spatial biology outlook can guide the design of effective combination drug strategies.
- Understanding molecular and microenvironmental factors is essential for comprehensive cancer treatment.
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