Preliminary findings of down-regulated genes in nasopharyngeal carcinoma

The cause and mechanism of nasopharyngeal carcinoma (NPC) progression are multifactorial and multigenic in nature. Despite the increasing number of genes found to be linked with NPC, the comprehensive list of associated genetic factors remains incomplete and the precise molecular pathways to this cancer are largely undefined. Here we show early evidence of possible association between several genes and the tumourigenesis of NPC. By employing the GeneFishingTM DEG Technique that allows the comparative analysis of expression profiles between normal and tumour nasopharyngeal biopsy tissues, we have identified 10 differentially expressed genes. These genes were down-regulated in tumours relative to normal control and have never been brought into the context of NPC tumourigenicity. Our findings represent preliminary yet novel clues of several associative genetic factors to neoplastic malignancy of the nasopharynx

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Functional roles of EMP-associated targets in breast cancer models

Epithelial mesenchymal plasticity in cancer generally refers to the ability of a cancer cell to transform into a different cell form, which facilitates the metastatic spread of a cancer. This thesis explores the roles of four cancer-associated genes that affect the transition of the cell state during cancer metastasis, and includes extensive research on two of the four gene targets, namely TRIM28 and TGFBI. The effects of these genes in breast cancer systems indicated great potential for improving therapeutic responses towards cancer drugs, which would alleviate the suffering of breast cancer patients

Targeting epithelial-mesenchymal plasticity in cancer: clinical and preclinical advances in therapy and monitoring

The concept of epithelial-mesenchymal plasticity (EMP), which describes the dynamic flux within the spectrum of phenotypic states that invasive carcinoma cells may reside, is being increasingly recognised for its role in cancer progression and therapy resistance. The myriad of events that are able to induce EMP, as well as the more recently characterised control loops, results in dynamic transitions of cancerous epithelial cells to more mesenchymal-like phenotypes through an epithelial-mesenchymal transition (EMT), as well as the reverse transition from mesenchymal phenotypes to an epithelial one. The significance of EMP, in its ability to drive local invasion, generate cancer stem cells and facilitate metastasis by the dissemination of circulating tumour cells (CTCs), highlights its importance as a targetable programme to combat cancer morbidity and mortality. The focus of this review is to consolidate the existing knowledge on the strategies currently in development to combat cancer progression via inhibition of specific facets of EMP. The prevalence of relapse due to therapy resistance and metastatic propensity that EMP endows should be considered when designing therapy regimes, and such therapies should synergise with existing chemotherapeutics to benefit efficacy. To further improve upon EMP-targeted therapies, it is imperative to devise monitoring strategies to assess the impact of such treatments on EMP-related phenomenon such as CTC burden, chemosensitivity/-resistance and micrometastasis in patients