In silico analysis and immunohistochemical characterization of NaPi2b protein expression in ovarian carcinoma with monoclonal antibody Mx35.

In silico analysis and immunohistochemical characterization of NaPi2b protein expression in ovarian carcinoma with monoclonal antibody Mx35.

Abstract
INTRODUCTION: Ovarian adenocarcinoma is frequently detected at the late stage, when therapy efficacy is limited and death occurs in up to 50% of the cases. A potential novel treatment for this disease is a monoclonal antibody that recognizes phosphate transporter sodium-dependent phosphate transporter protein 2b (NaPi2b).

MATERIALS AND METHODS: To better understand the expression of this protein in different histologic types of ovarian carcinomas, we immunostained 50 tumor samples with anti-NaPi2b monoclonal antibody MX35 and, in parallel, we assessed the expression of the gene encoding NaPi2b (SCL34A2) by in silico analysis of microarray data.

RESULTS: Both approaches detected higher expression of NaPi2b (SCL34A2) in ovarian carcinoma than in normal tissue. Moreover, a comprehensive analysis indicates that SCL34A2 is the only gene of the several phosphate transporters genes whose expression differentiates normal from carcinoma samples, suggesting it might exert a major role in ovarian carcinomas. Immunohistochemical and mRNA expression data have also shown that 2 histologic subtypes of ovarian carcinoma express particularly high levels of NaPi2b: serous and clear cell adenocarcinomas. Serous adenocarcinomas are the most frequent, contrasting with clear cell carcinomas, rare, and with worse prognosis.

CONCLUSION: This identification of subgroups of patients expressing NaPi2b may be important in selecting cohorts who most likely should be included in future clinical trials, as a recently generated humanized version of MX35 has been developed.

Activity and resistance of trastuzumab according to different clinical settings

Activity and resistance of trastuzumab according to different clinical settings: Publication year: 2012


Trastuzumab, a humanized monoclonal antibody directed against HER2, has shown efficacy in breast cancers; however many patients do not respond to this reagent. Here, we discuss the potential mechanisms of trastuzumab efficacy and resistance in different clinical settings as a step toward optimizing the appropriate application of this antibody. The three major antitumor mechanisms of trastuzumab, i.e., inhibition of proliferation, antibody-dependent cell cytotoxicity (ADCC) and inhibition of DNA repair, appear to be differentially operative in different clinical settings. ADCC appears to be the prevalent mechanism in trastuzumab neoadjuvant monotherapy, whereas in neoadjuvant, adjuvant or metastatic settings in which trastuzumab is combined with chemotherapy, the relative role of ADCC is probably small, considering the compromising effects of chemotherapy on the immune cells that mediate this mechanism. In neoadjuvant and adjuvant settings involving concomitant use of trastuzumab and chemotherapy, the primary mechanism at play is presumably inhibition of DNA repair by the antibody, while in sequential protocols, the antibody acts mostly by exerting cytostatic activity through inhibition of HER2-mediated tumor cell proliferation. According to the ability of the antibody to induce cytotoxic or cytostatic antitumor effects depending on the clinical setting, different criteria, i.e., RECIST for cytotoxic effect, OS, and DFS for cytostatic, must be considered in accurately estimating antibody efficacy. Moreover, since trastuzumab resistance likely depends directly on the mechanisms responsible for its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings.

phase 11 - Evaluation of TRC105 in the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma - Full Text View - ClinicalTrials.gov (not yet recruiting)

Biological: Chimeric monoclonal antibody (TRC105) to CD105

10 mg/kg weekly by intravenous administration on Days 1, 8, 15 and 22 of each 28-day cycle

Other Names:

• TRC105
• NSC#754227