Related Experiment Video
Updated: Jul 29, 2026
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Metabolic Response to Small Molecule Therapy in Colorectal Cancer Tracked with Raman Spectroscopy and Metabolomics
Gabriel Cutshaw1,2, Neeraj Joshi3, Xiaona Wen2
1Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
Abstract:
Despite numerous screening tools for colorectal cancer (CRC), 25 % of patients are diagnosed with advanced disease. Novel diagnostic technologies that are early, accurate, and rapid are imperative to assess the therapeutic efficacy of clinical drugs and identify new biomarkers of treatment response. Here Raman spectroscopy (RS) was used to track metabolic reprogramming in KRAS-mutant HCT116 and SW837 cells, and KRAS wild-type CC cells. RS combined with multivariate analysis methods distinguished nonresponsive, partially responsive, and responsive cells treated with cetuximab, a monoclonal antibody for EGFR inhibition, sotorasib, a clinically approved KRAS inhibitor, and various doses of trametinib, an inhibitor of the MAPK pathway. Cells treated with a combination of subtoxic doses of trametinib and BKM120, an inhibitor of the PI3K pathway, showed a synergistic response between the two pathways. Using a supervised machine learning regression model, we established a scoring methodology trained to a priori predict therapeutic response to new treatment combinations. RS metabolites were verified with mass spectrometry, and enrichment pathways were identified, including amino acid, purine, and nicotinate and nicotinamide metabolism that differentiated monotherapy from combination therapy. Our approach may ultimately be applicable to patient-derived primary cells and cultures of patient tumors to predict effective drugs for individualized care.
Insights
Raman spectroscopy (RS) can predict colorectal cancer (CRC) treatment response by analyzing metabolic changes. This method accurately distinguishes between responsive and nonresponsive cells, paving the way for personalized cancer therapy.
Area of Science:
- Biochemistry
- Oncology
- Spectroscopy
Background:
- Colorectal cancer (CRC) diagnosis often occurs at advanced stages, necessitating improved methods for assessing treatment efficacy.
- Novel diagnostic tools are crucial for identifying biomarkers of treatment response and guiding therapeutic strategies.
Purpose of the Study:
- To investigate the use of Raman spectroscopy (RS) for tracking metabolic reprogramming in colorectal cancer cells.
- To develop a predictive model for therapeutic response to targeted cancer therapies.
Main Methods:
- Raman spectroscopy (RS) was employed to analyze metabolic profiles of KRAS-mutant and wild-type colorectal cancer cells.
- Multivariate analysis and machine learning regression models were used to predict treatment response to cetuximab, sotorasib, trametinib, and BKM120.
- Metabolite identification and pathway enrichment analysis were performed using mass spectrometry.
Main Results:
- RS successfully differentiated between nonresponsive, partially responsive, and responsive colorectal cancer cells under various drug treatments.
- A synergistic response was observed with combination therapy targeting the MAPK and PI3K pathways.
- Metabolic pathways, including amino acid and purine metabolism, were identified as key differentiators between monotherapy and combination therapy.
Conclusions:
- Raman spectroscopy offers a rapid and accurate method for assessing therapeutic efficacy in colorectal cancer.
- The developed scoring methodology can predict patient response to new treatment combinations, enabling personalized cancer care.
- This approach holds potential for application in patient-derived primary cells and tumor cultures for individualized treatment selection.
More Related Videos
11:39Extraction of Aqueous Metabolites from Cultured Adherent Cells for Metabolomic Analysis by Capillary Electrophoresis-Mass Spectrometry
Published on: June 9, 2019
07:37An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
Published on: January 9, 2020
