Toward molecularly selected chemotherapy for advanced gastric cancer: State of the art and future perspectives
ABSTRACT In the last few years therapeutic options for gastric cancer patients have slowly, but constantly expanded following the introduction of both new chemotherapy agents and innovative indications for treatment. Along with the medical therapy also our knowledge of the molecular mechanisms underlying this disease has progressively improved. However although the available treatment options have undoubtedly increased no clear definitive indications can be made for a standard chemotherapy regimen and we are still unable to accurately select the appropriate treatment for the appropriate patient. Many molecular determinants of response/toxicity to chemotherapy agents have been identified, but only few of them seem to possess the necessary potential for a subsequent application in the clinical practice. Some of these factors have also been indicated as a therapeutic target for a novel class of anti-cancer compounds. This systematic review will analyse available data about these factors with the aim to constitute a starting point for future research.
- SourceAvailable from: Cherie Blenkiron
[Show abstract] [Hide abstract]
- "No [Scartozzi et al. 2009] "
ABSTRACT: Over the last 10 years there has been an explosion of information about the molecular biology of cancer. A challenge in oncology is to translate this information into advances in patient care. While there are well-formed routes for translating new molecular information into drug therapy, the routes for translating new information into sensitive and specific diagnostic, prognostic and predictive tests are still being developed. Similarly, the science of using tumor molecular profiles to select clinical trial participants or to optimize therapy for individual patients is still in its infancy. This review will summarize the current technologies for predicting treatment response and prognosis in cancer medicine, and outline what the future may hold. It will also highlight the potential importance of methods that can integrate molecular, histopathological and clinical information into a synergistic understanding of tumor progression. While these possibilities are without doubt exciting, significant challenges remain if we are to implement them with a strong evidence base in a widely available and cost-effective manner.rapeutic Advances in Medical Oncology, The 03/2010; 2(2):125-48. DOI:10.1177/1758834009360519
- [Show abstract] [Hide abstract]
ABSTRACT: Gastric cancer is a fatal human malignancy with poor prognosis. Modifications in gene expression, including those of the kallikrein-related peptidase family, have been portrayed in gastric carcinogenesis. Given KLK13 involvement in human malignancies, we aimed to uncover its prognostic strength in stomach cancer. Quantitative analysis of KLK13 profiles was accomplished in human gastric cancer cells and in a statistically significant sample size of stomach tissue specimens with the development of the highly sensitive real-time PCR methodology. Decreased KLK13 expression was demonstrated in cancerous compared with their matching non-malignant pairs (p=0.002) and in poorly differentiated gastric tumors (p=0.029). KLK13-positive patients were shown to live considerably longer (p=0.014) and with low risk of disease recurrences (p=0.043). This is the first study disclosing the possible clinical utility of KLK13 as a new tumor biomarker capable of predicting a favorable outcome for gastric cancer patients.Clinical biochemistry 10/2010; 43(15):1205-11. DOI:10.1016/j.clinbiochem.2010.07.016 · 2.28 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Increasing evidence is being reported regarding the hypothesis that several proinflammatory and anti-inflammatory cytokines may promote tumor progression and affect the host antitumor response. However, the manner in which a local cytokine network operates in tumor development remains unclear. We reviewed the literature to examine the consequences of novel insights into inflammatory cytokines associated with gastric cancer progression. The Medline and EMBASE databases were searched for publications regarding the role of inflammatory cytokines in the development of gastric cancer. A number of studies have suggested that several proinflammatory and anti-inflammatory cytokines promote tumor progression through the direct activation of nuclear factor-κB (NF-κB) and the upregulation of angiogenesis and adhesion molecules. Furthermore, these processes suppress host antitumor immunity, leading to tumor progression and metastasis. In patients with advanced gastric cancer, most cytokines that enhance or suppress host antitumor immunity appear to have elevated serum and local expression levels. The net cytokine environment fluctuates at various stages of tumor development. In conclusion, a more detailed understanding of the differential roles of malignant cell-derived and hostderived cytokines at different stages of the malignant process could, consequently, open new avenues for the manipulation of cytokine expression and function in cancer immunotherapy for gastric cancer.Gastric Cancer 11/2010; 13(4):212-21. DOI:10.1007/s10120-010-0568-x · 4.83 Impact Factor