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Published on: June 9, 2019
When cancer drug resistance meets metabolomics (bulk, single-cell and/or spatial): Progress, potential, and
Zhiqiang Zhang1,2, Chaohui Bao1, Lu Jiang1
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Resistance to drug treatment is a critical barrier in cancer therapy. There is an unmet need to explore cancer hallmarks that can be targeted to overcome this resistance for therapeutic gain. Over time, metabolic reprogramming has been recognised as one hallmark that can be used to prevent therapeutic resistance. With the advent of metabolomics, targeting metabolic alterations in cancer cells and host patients represents an emerging therapeutic strategy for overcoming cancer drug resistance. Driven by technological and methodological advances in mass spectrometry imaging, spatial metabolomics involves the profiling of all the metabolites (metabolomics) so that the spatial information is captured bona fide within the sample. Spatial metabolomics offers an opportunity to demonstrate the drug-resistant tumor profile with metabolic heterogeneity, and also poses a data-mining challenge to reveal meaningful insights from high-dimensional spatial information. In this review, we discuss the latest progress, with the focus on currently available bulk, single-cell and spatial metabolomics technologies and their successful applications in pre-clinical and translational studies on cancer drug resistance. We provide a summary of metabolic mechanisms underlying cancer drug resistance from different aspects; these include the Warburg effect, altered amino acid/lipid/drug metabolism, generation of drug-resistant cancer stem cells, and immunosuppressive metabolism. Furthermore, we propose solutions describing how to overcome cancer drug resistance; these include early detection during cancer initiation, monitoring of clinical drug response, novel anticancer drug and target metabolism, immunotherapy, and the emergence of spatial metabolomics. We conclude by describing the perspectives on how spatial omics approaches (integrating spatial metabolomics) could be further developed to improve the management of drug resistance in cancer patients.
Insights
Metabolic reprogramming is a key hallmark to overcome cancer drug resistance. Spatial metabolomics offers new insights into tumor heterogeneity and guides novel therapeutic strategies for improved cancer treatment.
Area of Science:
- Oncology
- Metabolomics
- Cancer Therapy
Background:
- Drug resistance is a major obstacle in cancer treatment, necessitating exploration of new therapeutic targets.
- Metabolic reprogramming is recognized as a crucial hallmark that can be targeted to overcome therapeutic resistance.
- Metabolomics and spatial metabolomics are emerging as powerful tools to understand and target metabolic alterations in cancer.
Purpose of the Study:
- To review the latest advancements in bulk, single-cell, and spatial metabolomics technologies for cancer drug resistance.
- To summarize metabolic mechanisms underlying cancer drug resistance.
- To propose strategies for overcoming cancer drug resistance using metabolomics approaches.
Main Methods:
- Review of current metabolomics technologies including mass spectrometry imaging for spatial metabolomics.
- Analysis of pre-clinical and translational studies on cancer drug resistance.
- Summary of metabolic mechanisms: Warburg effect, amino acid/lipid/drug metabolism, cancer stem cells, and immunosuppressive metabolism.
Main Results:
- Metabolomics enables targeting metabolic alterations to overcome drug resistance.
- Spatial metabolomics reveals tumor metabolic heterogeneity and drug-resistant profiles.
- Various metabolic mechanisms contribute to cancer drug resistance.
Conclusions:
- Spatial omics, integrating spatial metabolomics, holds promise for managing drug resistance in cancer patients.
- Targeting metabolic reprogramming is a viable strategy for therapeutic gain in cancer therapy.
- Early detection, response monitoring, and novel therapeutic targets are crucial for overcoming drug resistance.
