Highlights d We build the genomic and transcriptomic landscape of 465 primary TNBCs d Chinese TNBC cases demonstrate more PIK3CA mutations and LAR subtype d Transcriptomic data classify TNBCs into four subtypes d Multi-omics profiling identifies potential targets within specific TNBC subtypes

A better understanding of the biological roles and the pathological consequences of thiol-dependent enzymes has emerged in recent years, and hence considerable progress has been made in identifying and delineating cysteine proteases that can be considered promising drug targets from those involved in housekeeping functions. Cysteine proteases have been implicated in a wide variety of disease processes ranging from cardiovascular, inflammatory, viral and immunological disorders to cancer. The first milestone in drug development of cysteine protease inhibitors has probably been reached, as IDN-6556 (a broad spectrum caspase inhibitor) has recently received Orphan Drug label by the U.S. Food and Drug Administration for use in the treatment of the patients undergoing liver transplantation and other solid organ transplantation. IDN-6556, which blocks apoptosis, is in Phase II human clinical trial in patients undergoing liver transplantation. In addition, more than ten cysteine protease inhibitors are presently at various phases of clinical development/trials for diverse diseases. This review emphasises on the new development from the literature reports since the year 2000 in the exploration of potential cysteine proteases as prospective drug targets, and the investigation of promising inhibitors that can potentially be developed for the treatment of human diseases. Transglutaminases, another class of thiol-dependent enzymes, are not discussed here.

A photoelectrochemical sensing strategy for highly sensitive detection of small molecules was developed based on the recognition interaction between aptamer and target molecule-ATP.

Background: Patients with early stage breast cancer with lymph nodes metastasis were proven to have more aggressive biologically phenotypes. This study aimed to build a nomogram to predict lymph node metastasis in patients with T1 breast cancer. Methods: We identified female patients with T1 breast cancer diagnosed between 2010 and 2014 in the Surveillance, Epidemiology and End Results database. The patients were randomized into training and validation sets. Univariate and multivariate logistic regressions were carried out to assess the relationships between lymph node metastasis and clinicopathological characteristics. A nomogram was developed and validated by a calibration curve and receptor operating characteristic curve analysis. Result: Age, race, tumour size, tumour primary site, pathological grade, oestrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER2) status were independent predictive factors of positive lymph node metastasis in T1 breast cancer. Increasing age, tumour size and pathological grade were positively correlated with the risk of lymph node metastasis. We developed a nomogram to predict lymph node metastasis and further validated it in a validation set, with areas under the receiver operating characteristic curves of 0.733 and 0.741 in the training and validation sets, respectively. Conclusions: A better understanding of the clinicopathological characteristics of T1 breast cancer patients might important for assessing their lymph node status. The nomogram developed here, if further validated in other large cohorts, might provide additional information regarding lymph node metastasis. Together with sentinel lymph node biopsy, this nomogram can help comprehensively predict lymph node metastasis.

Groucho (Gro)/Transducin-like enhancer of split (TLE) family proteins act as co-repressors of many transcription factors, and are involved in key signaling pathways. TLE1 negatively regulates inflammation and has potential roles in various diseases, including cancer. Previous studies suggest TLE1 could be used as a diagnostic marker and is a possible therapeutic target in various malignancies. It is therefore important to elucidate the mechanisms underlying TLE1 function during cancer initiation and metastasis. In this review, we highlight the functions of TLE1 in cancer and explore targeted approaches for cancer diagnosis and treatment. In particular, we discuss the TLE1 function in pancreatic cancer.