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Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Identification of specific reachable molecular targets in human breast cancer using a versatile ex vivo proteomic
Vincent Castronovo1, Philippe Kischel, François Guillonneau
1Metastasis Research Laboratory, Center for Experimental Cancer Research, University of Liège, Liège, Belgium.
Abstract:
Targeting of tumoral tissues is one of the most promising approaches to improve both the efficacy and safety of anticancer treatments. The identification of valid targets, including proteins specifically and abundantly expressed in cancer lesions, is of utmost importance. Despite state-of-the-art technologies, the discovery of cancer-associated target proteins still faces the limitation, in human tissues, of antigen accessibility to suitable high-affinity ligands such as human mAb bound to bioactive molecules. Terminal perfusion of tumor-bearing mice or ex vivo perfusion of human cancer-bearing organs with a reactive biotin ester solution has successfully led to the identification of novel accessible biomarkers. This methodology is however restricted to perfusable organs, and excludes most of the tissues of interest to targeted therapies, e.g. primary breast cancer and metastases. Herein, we report on the development of a new chemical proteomic method that bypasses the perfusion step and thus offers the potential to identify accessible molecular targets in virtually all types of animal and human tissues. We have validated our new procedure by identifying biomarkers selectively expressed in human breast carcinoma. Overall, this powerful technology may lay the ground not only for custom-made therapies in cancer, but also for the development of therapies that need to be selectively delivered in a specific tissue.
Insights
Researchers developed a novel chemical proteomic method to identify accessible cancer biomarkers in all tissues, overcoming limitations of previous perfusion techniques for improved targeted cancer therapies.
Area of Science:
- Proteomics
- Chemical Biology
- Oncology
Background:
- Targeting tumor tissues enhances anticancer treatment efficacy and safety.
- Identifying accessible cancer-specific proteins is crucial for developing targeted therapies.
- Current methods like perfusion are limited to specific organs, excluding many cancers.
Purpose of the Study:
- To develop a new chemical proteomic method for identifying accessible molecular targets in any tissue.
- To overcome the limitations of perfusion-based methods in biomarker discovery.
- To enable the identification of novel accessible biomarkers for various cancers, including breast cancer.
Main Methods:
- Developed a novel chemical proteomic technique that bypasses the need for tissue perfusion.
- Applied the method to identify accessible biomarkers in human breast carcinoma.
- Validated the accessibility of identified biomarkers for potential therapeutic targeting.
Main Results:
- Successfully identified novel accessible biomarkers selectively expressed in human breast carcinoma.
- The new method demonstrated effectiveness in identifying biomarkers in non-perfusable tissues.
- The technology proved capable of identifying tissue-specific molecular targets.
Conclusions:
- The developed chemical proteomic method offers a powerful tool for discovering accessible molecular targets across diverse tissues.
- This technology facilitates the development of custom-made cancer therapies and targeted drug delivery systems.
- It expands the scope of biomarker discovery for improved precision oncology.
