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Mapping molecular networks using proteomics: a vision for patient-tailored combination therapy
Emanuel F Petricoin1, Verena E Bichsel, Valerie S Calvert
1US Food and Drug Administration-National Cancer Institute Clinical Proteomics Program, Office of Cellular and Gene Therapy, Center for Biologics Evaluation and Research, FDA, Bethesda, MD, USA. epetrico@gmu.edu
Summary
Molecular profiling using proteomic technology is key for personalized cancer therapy. This approach maps tumor protein networks to guide individualized treatment strategies for better patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Cancer is characterized by dysregulated intracellular and extracellular signaling cascades.
- Protein signaling circuits are primary targets for molecular cancer therapies.
- Tumor heterogeneity necessitates individualized treatment approaches.
Purpose of the Study:
- To highlight the critical role of in vivo tumor cell protein network mapping for patient-tailored molecular therapy.
- To demonstrate the feasibility of proteomic technology for molecular profiling in clinical settings.
- To present a vision for individualized combinatorial therapy based on proteomic data.
Main Methods:
- Utilizing emerging proteomic technology alongside genomic analysis for molecular profiling.
- Quantifying the activation state of kinase-driven signal networks through proteomic analysis.
- Analyzing post-translational phosphorylation data from clinical research specimens.
Main Results:
- Proteomic technology enables quantification of kinase pathway activation states.
- Phosphorylation data provides insights not obtainable through gene arrays.
- Case studies demonstrate the feasibility of generating critical data for individualized therapy.
- Potential new pathway interconnections, including differences between primary and metastatic lesions, can be revealed.
Conclusions:
- Proteomic mapping of tumor cell protein networks is essential for advancing personalized cancer medicine.
- Individualized therapy, guided by proteomic profiling, offers a solution to treatment non-responsiveness.
- This technology facilitates the clinical adoption of molecular stratification for targeted cancer treatments.