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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Adaptive protein and phosphoprotein networks which promote therapeutic sensitivity or acquired resistance
1‡Department of Biological Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A.
Abstract:
Despite the emergence of dozens of oncogenic targets and corresponding molecularly targeted therapies, in most cases tumours continue to progress or recur due to therapeutic resistance. In the present review, we highlight the ability of MS-based phosphoproteomics to quantify oncogenic signalling networks driving tumour growth and invasion, as well as those networks enabling tumour cell survival in the presence of chemotherapeutics. Quantitative protein phosphorylation profiling will facilitate the design and development of optimal therapeutic strategies targeting the initial tumour while simultaneously blocking the predominant resistance mechanisms.
Insights
Mass spectrometry-based phosphoproteomics can identify cancer signaling networks driving tumor growth and resistance. This approach aids in developing targeted therapies to overcome treatment failure.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Cancer therapies often fail due to therapeutic resistance, leading to tumor progression and recurrence.
- Existing molecularly targeted therapies face limitations in overcoming resistance mechanisms.
Purpose of the Study:
- To review the application of mass spectrometry-based phosphoproteomics in quantifying oncogenic signaling networks.
- To highlight the role of phosphoproteomics in understanding tumor growth, invasion, and survival under therapy.
Main Methods:
- Utilizing mass spectrometry (MS)-based phosphoproteomics to quantitatively profile protein phosphorylation.
- Analyzing signaling networks associated with tumor development and therapeutic resistance.
Main Results:
- MS-based phosphoproteomics can identify key signaling pathways driving tumor progression and invasion.
- This technique reveals networks crucial for tumor cell survival during chemotherapy.
Conclusions:
- Quantitative protein phosphorylation profiling is essential for designing effective cancer treatments.
- Targeting both initial oncogenic drivers and resistance mechanisms simultaneously is crucial for therapeutic success.
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