A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation.

Breast tumors that express p95HER2 are resistant to trastuzumab and may require alternative or additional anti-HER2-targeting strategies.

Background: Inflammation influences cancer development and progression. An elevated platelet to lymphocyte ratio (PLR), a marker of inflammation, has been linked to poor prognosis in several malignancies. Here, we quantify the prognostic impact of this biomarker.Methods: A systematic review of databases was conducted to identify publications exploring the association of blood PLR and overall survival (OS) in solid tumors. Data were pooled in a meta-analysis. Pooled HRs for OS by disease group and by PLR cutoff groups were computed and weighted using generic inverse-variance and random-effect modeling.Results: Twenty studies comprising 12,754 patients were assessed. Cutoffs for PLR defining risk groups ranged from 150 to 300 and were dichotomous (12 studies; group 1) or split into three groups (<150/150-300/ >300, 8 studies; group 2). Higher PLR was associated with significantly worse OS in group 1 [HR ¼ 1.87; 95% confidence interval (CI, 1.49-2.34); P < 0.001] and with a nonsignificant association in group 2 (HR per higher category ¼ 1.21; 95%CI, 0.97-1.50; P ¼ 0.10). The size of effect of PLR on OS was greater for metastatic disease (HR [group 1] ¼ 2.0; 95% CI, 1.6-2.7; HR [group 2] ¼ 1.6; 95% CI, 1.1-2.4) than for early-stage disease (HR [group 1] ¼ 1.5; 95% CI, 1.0-2.2; HR [group 2] ¼ 1.0; 95% CI, 0.8-1.3). A significant association was observed for colorectal, hepatocellular, gastroesophageal, ovarian, and pancreatic carcinoma in group 1 and for colorectal cancers in group 2.Conclusion: A high PLR is associated with worse OS in various solid tumors. Further research of its regulation and relevance in daily practice is warranted.Impact: PLR is a readily available and inexpensive biomarker with independent prognostic value in solid tumors. Cancer Epidemiol Biomarkers Prev; 23(7); 1204-12. Ó2014 AACR.

The cumulative toxicity of aromatase inhibitors when used as up-front treatment may explain the lack of overall survival benefit despite improvements in disease-free survival. Switching from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the best balance between efficacy and toxicity.

No abstract

Expression of high levels of immune cells including neutrophils has been associated with detrimental outcome in several solid tumors and new strategies to decrease their presence and activity are currently under clinical development. Here, we review some of the relevant literature of the role of neutrophils in different stages of the oncogenic process including tumor initiation, growth, proliferation or metastatic spreading and also focus on how neutrophil counts or the neutrophil-to-lymphocyte ratio may be used as a prognostic and predictive biomarker. Strategies to avoid the deleterious effects of neutrophils in cancer and to reduce their activity are discussed. Examples for such strategies include inhibition of CXCR1 and CXCR2 to decrease migration of neutrophils to tumoral areas or the inhibition of granulocyte colony stimulating factor to decrease the amount of neutrophils which has shown efficacy in preclinical models.

Docetaxel in combination with prednisone is the standard of care in men with symptomatic castration-resistant prostate cancer (CRPC). However, a substantial proportion of men with CRPC do not benefit from docetaxel or other systemic therapy and those who do benefit invariably progress and die of (or with) prostate cancer. Resistance to chemotherapy in metastatic CRPC is a result of cellular mechanisms of drug resistance intrinsic to prostate cancer and general mechanisms common to different tumor types. Continued signaling from the androgen receptor, activation of oncogenic survival pathways by various receptor tyrosine kinases and crosstalk between the androgen receptor and these oncogenic survival pathways are hallmarks of progression of CRPC. General mechanisms of drug resistance include the existence of subpopulations of cancer cells with cellular mechanisms of resistance, resistance related to interactions between prostate cancer cells and their surrounding microenvironment and impaired drug delivery to the cancer cells. New therapeutics targeting these mechanisms are under evaluation in clinical trials. Drug resistance in metastatic CRPC is multifactorial and complex and development of new medical therapies remains challenging.

Dasatinib is a small molecule tyrosine kinase inhibitor that targets a wide variety of tyrosine kinases implicated in the pathophysiology of several neoplasias. Among the most sensitive dasatinib targets are ABL, the SRC family kinases (SRC, LCK, HCK, FYN, YES, FGR, BLK, LYN, and FRK), and the receptor tyrosine kinases c-KIT, platelet-derived growth factor receptor (PDGFR) a and b, discoidin domain receptor 1 (DDR1), c-FMS, and ephrin receptors. Dasatinib inhibits cell duplication, migration, and invasion, and it triggers apoptosis of tumoral cells. As a consequence, dasatinib reduces tumoral mass and decreases the metastatic dissemination of tumoral cells. Dasatinib also acts on the tumoral microenvironment, which is particularly important in the bone, where dasatinib inhibits osteoclastic activity and favors osteogenesis, exerting a bone-protecting effect. Several preclinical studies have shown that dasatinib potentiates the antitumoral action of various drugs used in the oncology clinic, paving the way for the initiation of clinical trials of dasatinib in combination with standard-of-care treatments for the therapy of various neoplasias. Trials using combinations of dasatinib with ErbB/HER receptor antagonists are being explored in breast, head and neck, and colorectal cancers. In hormone receptor-positive breast cancer, trials using combinations of dasatinib with antihormonal therapies are ongoing. Dasatinib combinations with chemotherapeutic agents are also under development in prostate cancer (dasatinib plus docetaxel), melanoma (dasatinib plus dacarbazine), and colorectal cancer (dasatinib plus oxaliplatin plus capecitabine). Here, we review the preclinical evidence that supports the use of dasatinib in combination for the treatment of solid tumors and describe various clinical trials developed following a preclinical rationale. Clin Cancer Res; 17(17); 5546-52. Ó2011 AACR.