Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.     

Targeting PIK3CA Alterations in Hormone Receptor-Positive,Human Epidermal Growth Factor Receptor-2–Negative Advanced Breast Cancer: New Therapeutic Approaches and Practical Considerations

The phosphatidylinositol-3-kinase (PI3K) pathway is frequently dysregulated in human breast cancer. Approximately 30% of all patients with breast cancer will carry mutations of the PIK3CA gene, which encodes the PI3K catalytic subunit isoform p110α. Mutations in PIK3CA have been associated with resistance to endocrine therapy, HER2-directed therapy, and cytotoxic therapy. Early trials of pan-PI3K inhibitors showed little treatment benefit as monotherapy owing to disease resistance arising through enhanced estrogen receptor pathway signaling. Combining PI3K inhibition with endocrine therapy can help overcome resistance. Clinical trials of pan-PI3K inhibitors combined with endocrine therapy demonstrated modest clinical benefits but challenging toxicity profiles, facilitating the development of more selective PI3K-targeting agents. More recent trials of isoform-specific PI3K inhibitors in patients with PIK3CA mutations have shown promising clinical efficacy with a predictable, manageable safety profile. In the present review, we discuss the clinical relevance of mutations of PIK3CA and their potential use as a biomarker to guide treatment choices in patients with HR⁺ HER2⁻ advanced breast cancer.     

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis

Background

Symptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS).

Expression and clinical significance of FOS-like antigen 1 in gastric adenocarcinoma

BackgroundThe overexpression of FOS-like antigen 1 (FOSL1) in several types of cancers was reported before. However, the expression and clinical significance of FOSL1 in gastric cancer (GC) have not been elucidated.Materials and methodsThe expression of FOSL1 in 105 cases of GCs was detected with immunohistochemistry, and the mRNA of FOSL1 was investigated with quantitative real-time polymerase chain reaction(qRT-PCR) in 15 pairs of GCs and tumor adjacent tissues. With Chi-square test or Fisher test, we analyzed the correlation between FOSL1 expression and clinicopathological factors. With univariate analysis, we evaluated the correlations between clinicopathological factors including FOSL1 and overall survival (OS) rates. With multivariate analysis, we identified the independent prognostic risk factors of GC.ResultsThe percentages of patients with low and high FOSL1 expression in our study accounted for 43.81% and 56.19%, respectively. The mRNA levels of FOSL1 in GCs were significantly higher than those in tumor adjacent tissues. FOSL1 expression was demonstrated to be significantly correlated with lymphatic invasion (P = 0.036) and TNM stage (P = 0.016). High expression of FOSL1 was significantly correlated with lower 5-year OS (P = 0.002), and FOSL1 expression was identified as an independent prognostic biomarker of GC (P = 0.001).ConclusionsFOSL1 is an independent prognostic biomarker of GC. Detecting FOSL1 expression could help stratify GC patients with high-risk and guide the precious treatment.