Proteomic and metabolic prediction of response to therapy in gastric cancer

Abstract

Several new treatment options for gastric cancer have been introduced but the prognosis of patients diagnosed with gastric cancer is still poor. Disease prognosis could be improved for high-risk individuals by implementing earlier screenings. Because many patients are asymptomatic during the early stages of gastric cancer, the diagnosis is often delayed and patients present with unresectable locally advanced or metastatic disease. Cytotoxic treatment has been shown to prolong survival in general, but not all patients are responders. The application of targeted therapies and multimodal treatment has improved prognosis for those with advanced disease. However, these new therapeutic strategies do not uniformly benefit all patients. Predicting whether patients will respond to specific therapies would be of particular value and would allow for stratifying patients for personalized treatment strategies. Metabolic imaging by positron emission tomography was the first technique with the potential to predict the response of esophago-gastric cancer to neoadjuvant therapy. Exploring and validating tissue-based biomarkers are ongoing processes. In this review, we discuss the status of several targeted therapies for gastric cancer, as well as proteomic and metabolic methods for investigating biomarkers for therapy response prediction in gastric cancer.

Keywords: Gastric cancer; Matrix-assisted laser desorption-ionization; Positron emission tomography; Response prediction; Therapy.

Figure 1

Principle of matrix-assisted laser desorption-ionization imaging mass spectrometry. A section is cut from frozen tissue and prepared for mass spectrometry by coating with matrix solution. Energy for desorption and ionization is supplied by a pulsed laser beam. For each point in the user-defined measurement grid, a mass spectrum is generated by MALDI-TOF MS[79]. Copyright © 2009, Rights Managed by Nature Publishing Group. MALDI: Matrix-assisted laser desorption-ionization; TOF: Time-of-flight; MS: Mass spectrometry.

Figure 2

Matrix-assisted laser desorption-ionization imaging mass spectrometric profiles of breast and gastric cancer tissues. Human epidermal growth factor receptor-2 (HER2)-status can be identified on a proteomic level across different cancer types suggesting that HER2 overexpression may constitute a unique molecular event independent of the tumor site[65]. Reprinted with permission from [65]. Copyright © 2010 American Chemical Society.

Figure 3

Positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose studies in patients with clinically responding and nonresponding tumors[75]. A: In the responding tumor, fluorodeoxyglucose (FDG) uptake decreases to background level 14 d after initiation of chemotherapy; B: In contrast, FDG uptake is almost unchanged for the nonresponding tumor. Copyright © 2003 American Society of Clinical Oncology.