Clinical application of proteomics in ovarian cancer prevention and treatment.

摘要

As recent scientific findings using whole-genome mutational scanning technologies have concluded, cancer is a protein pathway disease, which is often diagnosed too late, when the success of therapeutic modalities is very limited. Proteomics has been proposed as the field that can help overcome this limitation and usher in a new era of molecular investigation for early diagnosis and classification of tumors. Proteomics applications in cancer research encompass two general aspects: (i) the study and characterization of protein production; and (ii) the definition of protein function. The first aims to identify qualitative or quantitative differences in the proteome that can help differentiate between healthy and diseased states or achieve a better clinical classification of diseases. The second studies the complexity of protein interactions and their activation states, mapping the network of signaling pathways within and outside the cells. The challenges in translating the findings of proteomics research into clinical practice are numerous. Lack of reproducibility, variable availability of samples and the bias associated with their selection and handling, the need for large, prospective validation trials, and finally the strict requirement for a very high level of clinical sensitivity and specificity are some of the hurdles that need to be overcome to achieve early detection and treatment. Nevertheless, proteomics is a field in rapid progression that has already developed beyond initial criticism and is making its way toward important applications and discoveries. Specifically, there has been an increasing number of reports on the potential clinical application of proteomics for early detection as well as risk assessment and management of ovarian cancer. This disease is the leading cause of death from gynecologic malignancies in the US, with poor prognosis resulting from the lack of reliable, sensitive screening tests and the limited understanding of the mechanisms of chemoresistance and relapse. In the future, serum proteomics applications in the gynecologic oncology field could identify blood-based biomarkers that are predictors of disease presence or progression, and tissue proteomics could help define the optimal targeted agent and effective dose for each patient's disease. These advances will allow improved monitoring of therapy response and disease relapse, and aid in the engineering of new drugs and strategies to circumvent resistance mechanisms while avoiding the adverse effects of traditional chemotherapy.