Proteomic profiling in ovarian cancer

Abstract

Objective: To describe the role of proteomic profiling in the diagnosis and treatment of ovarian cancer.

Methods: We report a thorough review of the literature, ongoing trials, and our group's experience with proteomic profiling for early detection, recurrence, and treatment of ovarian cancer.

Results/conclusions: Ovarian cancer remains the deadliest gynecologic malignancy in the western world and is most often diagnosed at a rarely curable late stage. Novel applications of proteomic techniques, such as mass spectrometry, show promise in the quest for reliable multimodality screening programs for the early detection of ovarian cancer. Proteomic analysis of tissue samples has underscored the heterogeneity of this disease process. Development of validated assays that survey the genetic and/or proteomic makeup of an individual tumor will add greatly to the histological classification of the tumor and may lead to different treatment approaches tailored to the unique expression pattern of each individual patient. As novel agents that disrupt signal propagation develop, proteomic profiling by reverse-phase protein arrays can characterize the in-tumor efficacy of the agent by quantification of the changes in expression levels of activated proteins. Together, better understanding of the potential diagnostic and therapeutic targets followed with proof-of-target effect will lead to rational combinations of novel therapy and improve individual ovarian cancer patient outcome.

FIGURE 1.

Tissue proteomics for the discovery of novel combinations of signal transduction inhibitors. Proteomic analysis of tissue: tumor biopsies, patient serum, effusion samples, and so on reveals key biochemical pathways involved in cell survival. Rational combination of signal transduction inhibitors targets these pathways for more efficient tumor inhibition.

FIGURE 2.

SELDI-TOF. A commercial chip customized with specific bait molecules chemically binds protein samples or uses an antibody to which samples bind. A laser is focused on the captured protein, converting it to the gaseous phase that passes through a tube to a detector plate, where the mass-to-charge ratio is determined.

FIGURE 3.

Translational proteomic analysis during treatment on a clinical trial. Serial biopsies are taken before treatment, after treatment with a single agent, and after treatment with both agents to determine biochemical signaling changes in the tumor during treatment. After the computed tomography—guided biopsy is performed, the sample is immediately frozen. Subsequently, the sample is subjected to reverse-phase tissue lysate array.