Currently available molecular analyses for personalized tumor therapy (Review).

Targeted therapies are becoming more common and genetic tumor profiling is becoming more precise and affordable. The aim of the present review was to demonstrate the importance of molecular analyses in tumors, summarize the current situation, provide an outlook on how to improve diagnosis to facilitate individualized therapy, including the use of specific methodologies for tumor marker analysis to improve patient treatment. Most predicted metabolomic and proteomic biomarkers have not progressed from the laboratory to clinical trials, as most of the trials were stopped at the initial stage of biomarker identification. The use of liquid biopsies as a clinical tool improves cancer screening, diagnosis and prognosis; furthermore, is able to improve the classification of more diverse disease entities, assess therapy response and identify treatment-resistant clones, allowing for more stringent patient monitoring. Based on specific clinical populations and the unique molecular features of a cancer, the identification of a suitable targeted therapy may be accomplished. The present review provides insight into cancer genomic testing in the clinical setting and the available methods, supporting the prioritization of molecular therapeutic tumor targeting.

Interferon ß improves the efficacy of low dose cisplatin by inhibiting NF-κB/p-Akt signaling on HeLa cells.

The purpose of this study was to evaluate the anticancer efficacy of interferon ß in combination with low dose of cisplatin on human cervical cancer progression, as well as its principal action mechanism. The combination treatment synergistically potentiated the effect of interferon ß on cell growth inhibition and DNA damage on HeLa cells by repressing NF-κB/p-Akt signaling. Synergistic targeting of these pathways has a therapeutic potential. Further, the combination treatment ameliorated the expression of pro-apoptotic Bax, and decreased the expression of anti-apoptotic protein Bcl-2. Additionally, the expression of active PARP was significantly increased and MMP-9 level was decreased in combination group as compared to the expression seen for the treatment with interferon ß or cisplatin alone. Results demonstrate that the synergistic inhibitory effects of interferon ß and low dose of cisplatin on human cervical cancer cells and also suggest that the inhibition of NF-κB/p-Akt signaling pathway plays a critical role in the anticancer effects of combination treatment along with the induction of PARP. Therefore, the combination of interferon ß and cisplatin may be a useful treatment for human cervical cancer, with a greater effectiveness than other treatments.

Inhibitory effects of interferon-ß on hepatocellular carcinoma HepG2 via Akt/STAT phosphorylation.

Conventional chemotherapy fails to cure metastatic hepatoma mainly due to its high hepatotoxicity. Currently, doxorubicin is the most widely used drug against liver cancer either as single agent or in combination with other chemotherapeutics such as cisplatin. It is limited due to their severe toxicity on normal hepatocytes. Therefore, alternative therapeutic agents without or with low hepatotoxicity are highly desirable. Interferons are a family of cytokines that potently demonstrate antiviral, immunomodulatory, and antiproliferative activities. It also exerts direct cytotoxic effects on tumor cells. The purpose of this study was to examine the in vitro cytotoxicity of interferon-ß on HepG2 cells. We revealed the presence of binding receptor of interferon-ß in HepG2 cells. The dose-dependent inhibition on cell proliferation was observed. We demonstrated that IFN-ß exhibited significant cytotoxicity in HepG2 cells mainly through phosphorylation of signal transducers and activators of transcription 2. The activation of Akt was suppressed. The stimulation of pro-apoptotic protein expression of Bax, inhibition of anti-apoptotic protein expression of Bcl-2, activation of cleaved caspases 9 and 3 was found at increasing concentrations. In conclusion, our results suggest that interferon-ß has potential to inhibit cell proliferation dose dependently. Increased concentrations of interferon-ß influenced apoptosis via mitochondrial pathway through inhibition of p-Akt.

Synergistic anti-carcinogenic effect of interferon-ß with cisplatin on human breast adenocarcinoma MDA MB231 cells.

Cisplatin is one of the most commonly used chemotherapeutic agents for breast cancer treatment. However, its efficacy is greatly limited by its toxic side effects. The present study investigated the synergistic effect of interferon ß with cisplatin on MDA MB231 cells. The antiproliferative effect was measured by the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The combination index (CI) was calculated using the method of Chou and Talalay. Cytotoxicity was determined by trypan blue and clonogenic assay. Genotoxic and cytostatic effects were studied using micronucleus assay and nuclear division index (NDI). Protein expression was analyzed using immunoblotting. Interferon ß (100-2500 IU/mL) and Cisplatin (0.01-100 µM) had an inhibitory effect on the proliferation of cancer cells in a dose-dependent manner, with the IC50 values at 1500 IU/mL and 20 µM for interferon ß and cisplatin, respectively. Western blot analysis revealed expression of interferon ß binding receptor in MDA MB231 cells. More interestingly, synergistic, cytotoxic and genotoxic effects were observed after treatment with a combination of interferon ß with reduced dosage of cisplatin. Decreased expression of Bcl-2 and increased expression of Bax stimulated the cytochrome c release, which triggers caspase-9 and -3 activation significantly increased in the combinational group. In conclusion the combination of interferon ß with reduced dose of cisplatin results synergistically improved growth-inhibition and apoptosis-inducing effect on MDA MB231 cells.