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Background: Cancer Antigen 15-3 (CA 15-3) is a tumor-associated antigen used as serum marker for breast cancer surveillance in patients and for monitoring the response to treatment. Aim of this study was to retrospectively evaluate CA 15-3 as a prognostic factor in early detection of breast cancer relapse as well as to analyze the statistical correlation between CA 15-3 levels and clinical-pathological parameters including staging, grading, estrogen and progesterone receptors. Methods: Sera of 726 women with breast carcinoma obtained preoperatively and postoperatively were assayed for CA 15- 3 by chemoluminescent immunometric assay. Results: We found that the mean serum CA 15-3 levels in patients before surgery were significantly higher (36.59 U/ml) compared with those of CA 15-3 after surgery (27.11 U/ml). We also found that elevated preoperative serum levels of CA 15-3 were significantly correlated with the presence of metastatic disease. In particular, among 305/700 patients (43,6%) that displayed over cut-off (>40U/ml) preoperative levels of CA 15-3, 94 patients (30,8%) developed advanced disease (metastases to distant sites). By contrast, in a subgroup of 395/700 patients (56.4%) with CA 15.3 serum levels < 40U/ml, only 32/305 patients (8%) showed signs of advanced disease during follow-up. Cox regression analysis revealed that only the presence of metastasis and the increased serum levels of CA 15-3 after surgery are significant risk factors for relapse of disease. Conclusion: Elevated preoperative concentrations of CA 15-3 may be a useful predictive factor for cancer progression in postoperative patients.

Hepatocellular carcinoma (HCC) is a cancer that usually develops on a liver already compromised by cirrhosis. Study of the underlying molecular mechanisms is essential so as to improve therapeutic strategies and to develop new pharmacological agents that may prevent or improve the course of this malignancy. Transforming growth factor-beta (TGF-β) intervenes in the process of hepatic fibrogenesis and cirrhosis, two pathogenic preconditions for the formation and progression of HCC [1] [2]. In addition, TGF-β plays a crucial role in the molecular pathogenesis of HCC and may, therefore, prove to be a promising drug target. We and other authors have recently demonstrated that inhibition of the TGF-β signaling pathway results in a synergistic downstream action with an inhibitory effect on the progression of HCC. Several TGF-β inhibitors have recently been developed, most of which are still in a preclinical phase, but they may soon be available for testing in patients with HCC. However, well-designed clinical trials will be needed to evaluate the effectiveness of these new agents prior to routine use in the clinic. Aim of this article is to make a brief review of the benefits and limitations of targeting the TGF-β signaling pathway in HCC.

The metastatic spread of cancer is still the major barrier to the treatment of this disease. Understanding the molecular mechanisms underlying the metastatic process is of crucial importance to tune novel therapeutic strategies aimed at contrasting the dissemination of cancer. Metastasis is a sequential multistep process that ultimately leads to the cancer's outgrowth in a different organ from which it had originated. This clinically and experimentally involves the following steps: invasion of adjacent tissues, intravasation, transport of cancer cells through the circulatory system, arrest at a secondary site, extravasation and growth in a secondary organ. Additionally, tumor growth and metastasis depend on the ability of the tumor to induce its own blood supply through angiogenesis. Each of these steps can potentially be targeted by therapeutic agents, but the limited knowledge regarding the molecular events of metastasis makes most therapeutic strategies largely inefficient. However, important methodological advances have recently led to further insights into the biology of metastasis, thus raising the possibility of designing more appropriate pharmacological strategies to contrast the specific steps of the metastatic process. A variety of pharmacological approaches including inhibition of tumor invasion, angiogenesis, signal transduction pathways, and most recently the targeting of tumor stroma, are now under fervent development. Benefits and limits of these approaches, as well as, new therapeutic opportunities are herein discussed. Agents that limit any phase of the metastatic process may be therapeutically useful. Therefore, the future pharmacological challenge will be to combine drugs that target different aspects of this complex multistep process.