PI3K/AKT/mTOR inhibitors as potential extracellular matrix modulators for targeting EMT subtype gastric tumors.

Targeting the extracellular matrix (ECM) is considered as a promising strategy in cancer therapeutics. This study was designed to identify the potential ECM modulators for gastric cancer therapeutics. Exploration of the expression profiles of gastric tumors revealed the elevated expression of ECM genes in gastric tumor tissues compared to the adjacent normal tissues with increased expression in diffuse subtype gastric tumors and specifically in epithelial to mesenchymal transition (EMT) molecular subtype tumors.

OCT4-mediated transcription confers oncogenic advantage for a subset of gastric tumors with poor clinical outcome.

Deregulated transcription programs and signaling pathways are the critical factors involved in the process of carcinogenesis. Signaling pathway-based classification of tumors is expected to pave the way for the development of targeted therapeutics. We investigated the OCT4-mediated transcription program in the gene expression profiles of 939 gastric tumor samples.

Calcium channel blockers lercanidipine and amlodipine inhibit YY1/ERK/TGF-β mediated transcription and sensitize the gastric cancer cells to doxorubicin.

Elevated expression of YY1 is known to confer anti-apoptotic phenotype and hence is an attractive target for cancer therapeutics. In a repurpose screening, towards the identification of the inhibitors of YY1 regulated transcription in gastric cancer cells, the calcium channel blockers lercanidipine and amlodipine have been identified to inhibit YY1 more efficiently. We further probed these calcium channel blockers for their potential feature of alleviating the drug resistance in gastric cancer cells.

YY1 regulated transcription-based stratification of gastric tumors and identification of potential therapeutic candidates.

Gastric cancer is one of the leading causes of cancer-related death worldwide. The transcription factor YY1 regulates diverse biological processes, including cell proliferation, development, DNA damage responses, and carcinogenesis. This study was designed to explore the role of YY1 regulated transcription in gastric cancer.

Development of a cell-based pathway modulator screening system to screen the targeted cancer therapeutic candidates.

To overcome the issues of poor prognosis and to tackle the non-responsiveness to various chemotherapeutics; it is necessary to develop targeted cancer therapeutic agents. Also, it is being necessary to understand the molecular targets of the drug candidates and drugs in the context of cellular signaling pathways, to make progress towards the development of targeted cancer therapeutics. Towards addressing these, we have established a cell-based and pathway-focused drug screening system for the pathways such as MYC, E2F, WNT, ERK, NRF1/2, HIF1α, p53, YY1 and NFκB.

Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients.

The identification of new drugs for the targeted therapy of gastric cancer remains an important need. The RAS/RAF/MEK/ERK/ELK1 signaling cascade is activated in many cancers, including gastric cancer. To identify the targetable inhibitors of the ERK/MAPK pathway, we performed a repurposing screening of a panel of antimicrobial agents in gastric cancer cells using an ERK/MAPK-driven firefly luciferase reporter assay.

Abacavir induces the transcriptional activity of YY1 and other oncogenic transcription factors in gastric cancer cells.

Yin Yang 1 (YY1) is a ubiquitous transcription factor with both transcriptional activating and repressing functions. Targeting YY1 is considered as a potential therapeutic strategy for several malignancies. Telomerase Reverse Transcriptase (TERT) is also considered as a potential target for cancer therapeutics.

Coexpressed modular gene expression reveals inverse correlation between immune responsive transcription and aggressiveness in gastric tumours.

The existing large number of gene expression profiles of tumour samples offers a great advantage for the integrative functional genomic exploration of molecular dysregulation in cancers. The clusters of genes (modules) derived from a gastric cancer (GC) coexpression network were explored to understand their clinical and functional significance. Among the modules derived from the GC mRNA expression network, six modules were relatively highly expressed in diffuse type gastric tumours.