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Insulin-like growth factor receptor 1 (IGF-1R) with its ligands and intracellular pathway is involved in cell growth and survival control. Many studies have shown how IGF-1R is over-expressed in various tumor cell lines and histological samples. In recent years many trials have been conducted investigating IGF-1R as a possible cancer therapy, with major efforts focusing on the use of monoclonal antibodies and small molecules directed against the IGF-1R-driven pathway. Several drugs are currently under intense investigation and in different experimental phases. Available data suggest that this class of drugs is well tolerated with mild to moderate side effects, when used alone or in combination with other therapeutic agents. The efficacy profile seems to be promising. However, further studies are needed to define the exact role of IGF-1R inhibitors in clinical practice.

The significance of phosphorylated mTOR (p-mTOR) expression is unknown in triple-negative breast carcinoma (TNBC). The aims of the present study were to assess the expression of p-mTOR in early TNBC and to evaluate possible correlations between androgen receptor (AR) expression, clinicopathological parameters and disease outcome. Between January 2009 and December 2013, all consecutive patients who were diagnosed and completed the treatment of invasive TNBC at our institution were eligible for this analysis. Patients with stage IV disease were excluded. The evaluation of p-mTOR immunohistochemical staining was semi-quantitatively considering both the percentage of positive tumor cells (range, 0-100%) and staining intensity (range, 0-3+). Ninety-eight TNBC patients were included. Approximately 33% of cases were p-mTOR positive and there was no association between positive immunostaining for p-mTOR and DFS (p=0.74) and OS (p=0.81). p-mTOR positivity was associated with small tumor size (p=0.03) and AR expression (p=0.04). High expression of p-mTOR may drive tumor proliferation in almost one third of TNBC. The biological association between mTOR activation and AR pathway suggests that there may exist a subgroup of TNBC in which the combination of both AR antagonism and mTOR inhibition should have a synergistic effect on cell growth and tumor progression.

The number of anti-angiogenic drugs who demonstrated activity in metastatic colorectal cancer patients is arising but there is still much debate on which is the optimal use of this class of agents, with particular emphasis given on when (meant as in which line of treatment) and how (meant as in duration of treatment). We sampled the data of randomised phase II-III trials employing this type of drugs, with particular emphasis on trying to "highlight" situations where anti-angiogenetic treatment could provide most benefit. The review displays all relevant clinical data regarding the use of anti-angiogenic drugs in metastatic colorectal cancer and comments on potential implications of these trials in everyday clinical practice. © 2014 Elsevier Ltd.

BACKGROUND:The potential clinical impact of aspirin use beyond its canonical indications is a novel matter of scientific debate. In patients with metastatic colorectal cancer failing all available options, regorafenib and TAS 102 represent the only chance of treatment. Although effective, these therapeutic options bring along a not-negligible burden in terms of economic costs and toxicity. In this setting, the indication to use aspirin in combination with chemotherapy would potentially represent a medical revolution under the economic and toxicity profile.PATIENTS AND METHODS:We assessed the role of aspirin in patients with metastatic colorectal cancer who failed all previous treatments and were receiving capecitabine as a salvage option before the introduction of regorafenib and TAS-102.RESULTS:Sixty-six patients were eligible. Twenty patients (30%) were on incidental treatment with aspirin for cardiovascular diseases. Twelve (60%) partial responses were seen in patients on treatment with aspirin, compared with 3 (6%) partial responses in the remaining patients (P = .00007). Sixteen patients on aspirin (80%) obtained disease control versus 14 (30%) patients who were not on aspirin (P = .000377). The median progression-free survival for patients receiving treatment with aspirin was 6.5 months versus 3.3 months for patients who were not on aspirin (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .0042). A significantly improved overall survival was also evident in aspirin users (median overall survival, 14.7 vs. 8.7 months, respectively; hazard ratio, 0.43; 95% confidence interval, 0.26-0.72; P = .0023).CONCLUSION:Aspirin may improve the clinical outcome of heavily pre-treated patients with metastatic colorectal cancer receiving chemotherapy. Further studies are necessary before application in the clinical practice.Copyright © 2016 Elsevier Inc. All rights reserved.KEYWORDS:Aspirin; Capecitabine; Chemotherapy; Colon cancer; Salvage treatment

Background: There is a growing body of evidence that immune response plays a large role in cancer outcome. The neutrophil to lymphocyte ratio (NLR) has been used as a simple parameter of systemic inflammation in several tumors. The purpose was to investigate the association between pre-treatment NLR, disease-free survival and overall survival in patients with early triple negative breast cancer (TNBC). Methods: We reviewed the records of patients with stage I-III TNBC at our Institution from 2006 to 2012. The association between pre-treatment NLR and survival was analyzed. The difference among variables was calculated by chi-square test. DFS and OS were estimated using Kaplan-Meier method. Cox analysis was performed to analyze clinical parameters for their prognostic relevance. Results: A total of 90 patients were eligible. There was no significant correlation among pre-treatment NLR and various clinical pathological factors. Patients with NLR higher than 3 showed significantly lower DFS (p = 0.002) and OS (p = 0.009) than patients with NLR equal or lower than 3. The Cox proportional multivariate hazard model revealed that higher pre-treatment NLR was independently correlated with poor DFS and OS, with hazard ratio 5.15 (95% confidence interval [CI] 1.11-23.88, p = 0.03) and 6.16 (95% CI 1.54-24.66, p = 0.01) respectively. Conclusion: Our study suggests that pre-treatment NLR may be associated with DFS and OS patients with early TNBC. Further validation and a feasibility study are required before it can be considered for clinical use.

Dalotuzumab (MK-0646; h7C10), being developed by Merck & Co Inc under license from Pierre Fabre SA, is a recombinant humanized IgG1 mAb against the IGFR1 for the potential intravenous treatment of cancer. Preclinical studies have demonstrated that dalotuzumab acts by inhibiting IGF-1- and IGF-2-mediated tumor cell proliferation, IGFR1 autophosphorylation and Akt phosphorylation. In multiple cancer cell lines and in mouse xenograft models, dalotuzumab displayed significant antitumor activity, in particular against NSCLC and breast cancer. In addition, coadministration of dalotuzumab with other anticancer agents, such as taxanes, enhanced the in vitro and in vivo antitumor activity of dalotuzumab. Preliminary data from phase I clinical trials suggest that dalotuzumab is safe, well tolerated and significantly inhibits tumor proliferation. At the time of publication, several clinical trials evaluating dalotuzumab, alone and in combination with other anticancer agents, were ongoing in patients with various types of solid tumor and in patients with multiple myeloma. Although preliminary results appear promising, only future clinical and translational data will clarify the best clinical setting and treatment combinations for the optimal use of dalotuzumab in clinical practice.