Identification of Novel Protein Biomarkers in the Era of Precision Medicine Oncology

Cancer is a leading cause of morbidity and mortality in developed countries including the United States. Early detection of various cancers, before they spread and become incurable, has been the best weapon in the war on cancer that began with the signing of the National Cancer Act in 1971. The premise of Precision Medicine is the ability to customize personalized medical care to individual patients through the incorporation of molecular profiles and clinical characteristics in treatment determination utilizing molecular diagnostics, and targeted therapies.

Proteins uniquely produced by tumors and their surrounding microenvironment constitute valuable biomarkers that aid in diagnosis of initial tumors, screening the population, monitoring of tumor progression, metastases, response to treatment and relapse (e.g., the prostate-specific antigen, PSA, is routinely used for screening and monitoring of prostate cancer). Moreover, some biomarkers can stratify patients into sub-groups that differ in their prognosis and response to different treatment options, which allows designing individual treatment plans. For instance, the human epidermal growth factor receptor 2 (Her2-neu) is overexpressed in about 20% of breast cancer patients and can be targeted by a monoclonal antibody called Herceptin in these patients, which enhances the overall survival when combined with chemotherapy.

Recent advances in Genomics and Proteomics allow for the de-novo identification of tumor-related biomarkers through differential expression analyses of the different steps of cancer progression. In our approach to biomarker discovery, we combine the techniques of laser capture microdissection, differential two- dimensional gel electrophoresis, and mass spectrometry to identify novel biomarkers of tumor progression for cervical cancer and other malignancies. These identified molecular markers have promising clinical utility in Precision Medicine Oncology.

Learning Objectives: 

1. Explain the role of Proteomics in Cancer Molecular Diagnostics.
2. Describe the experimental design behind the de-novo biomarker discovery approach combining laser capture microdissection, differential two- dimensional gel electrophoresis, and mass spectrometry to identify novel biomarkers of tumor progression.