Despite promising results in preclinical and clinical studies, the therapeutic efficacy of antiangiogenic therapies has been restricted by a narrow focus on inhibiting the growth of endothelial cells. Other cell types in the tumor stroma are also critical to the progression of cancer, including mural cells. Mural cells are vascular support cells that range in phenotype from pericytes to vascular smooth muscle cells. Although the role of pericytes and pericyte-like cells in the pathophysiology of cancer is still unclear, evidence indicates that aberrations in pericyte-endothelial cell signaling networks could contribute to tumor angiogenesis and metastasis. The purpose of this review is to evaluate critically recent evidence on the role of pericytes in tumor biology and discuss potential therapeutic targets for anticancer intervention. Am. J. Hematol. 85:593-598, 2010. V

Breast cancer is the most common in women worldwide, with some 5-10% of all cases due to inherited mutations of BRCA1 and BRCA2 genes. Obesity, hormone therapy and use of alcohol are possible causes and over-expression of leptin in adipose tissue may also play a role. Normally surgery, radiation therapy and chemotherapy allow a good prognosis where screening measures are in place. New hope in treatment measures include adjuvant therapy, neoadjuvant therapy, and introduction of mono-clonal antibodies and enzyme inhibitors.

Background The effectiveness of tyrosine kinase inhibitors (TKI) in preventing brain metastases in patients with renal cell carcinoma (RCC) is unclear. Methods Preclinical studies were conducted to determine the steady-state brain and plasma concentrations of sorafenib and sunitinib in mice deficient in the drug efflux transporters, p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). A single-institution retrospective analysis of patients treated from 2008 to 2010 was conducted to assess the incidence of brain metastases before and during TKI treatment Results Transport of sorafenib and sunitinib across the blood-brain barrier was restricted. Retrospective analysis revealed that median time to develop metastatic brain disease was 28 months (range:1-108) while on TKI therapy and 11.5 months (range:0-64) in patients not receiving TKI therapy. The incidence of brain metastases per month in patients not treated with TKI therapy was 1.6 higher than the incidence in patients treated with TKI therapy. Conclusions Penetration of sorafenib or sunitinib through intact blood-brain barrier to brain tissue is limited; however, the incidence of brain metastases per unit time is decreased in patients on TKI therapy in comparison to the “cytokine” era.

Introduction Oncolytic virus therapy is a promising therapy for numerous tumor types. Edmonston-strain measles virus (MV) has been tested in clinical trials for ovarian cancer, glioma, and myeloma. Therefore, the antitumor activity of MV against NSCLC was assessed. Methods Human NSCLC cells and immortalized lung epithelial cell lines, Beas2B, were infected with either MV producing GFP (MV-GFP) or MV producing carcinoembryonic antigen (MV-CEA). Cells were assessed for viability, induction of apoptosis by caspase and PARP cleavage, and for viral transgene production. The dependency of MV entry on CD46 and nectin-4 were determined using blocking antibodies. The role of host translational activity on viral replication was assessed by overexpression of eIF4E and translation inhibition. Antitumor activity was assessed by measuring treated NSCLC xenografts from flanks of nude mice. Results MV infection of NSCLC cells results in potent cell killing in most of the cell lines compared to immortalized Beas2B cells and induces apoptosis. MV infection was prevented by blocking of CD46, however was independent of nectin-4 blockade. Tumor weights are diminished following intratumoral injections of MV-CEA in 1 of 2 cell lines and result in detectable viral transgene in serum of mice. Conclusions These data indicate that MV is oncolytic for human NSCLC and this was independent of nectin-4 expression. Dysregulated protein translational machinery may play a role in determining tumor tropism in NSCLC. MV combined with gemcitabine could be explored further as chemovirotherapy for NSCLC.

Lung cancer is the leading cause of cancer-related deaths in the world. Conventional therapy for lung cancer is associated with lack of specificity and access to the normal cells resulting in cytotoxicity, reduced cellular uptake, drug resistance and rapid drug clearance from the body. The emergence of nanotechnology has revolutionized the treatment of lung cancer. The focus of nanotechnology is to target tumor cells with improved bioavailability and reduced toxicity. In the recent years, nanoparticulate systems have extensively been exploited in order to overcome the obstacles in treatment of lung cancer. Nanoparticulate systems have shown much potential for lung cancer therapy by gaining selective access to the tumor cells due to surface modifiability and smaller size. In this review, various novel nanoparticles (NPs) based formulations have been discussed in the treatment of lung cancer. Nanotechnology is expected to grow fast in future, and it will provide new avenues for the improved treatment of lung cancer. This review article also highlights the characteristics, recent advances in the designing of NPs and therapeutic outcomes.