Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings. Current treatment strategies in colorectal cancer are largely ‘one drug fit all’ model for patients that display same pathological conditions. However, CRC is a very heterogenous set of malignancy that does not support for above criteria. Each subtype displays different pathological and genetic signatures. Based on these features, therapeutic stratification for individual patients may be designed, which may ultimately lead to improved therapeutic outcomes. In this comprehensive review, we have attempted to briefly outline major CRC pathways. A detailed overview of molecular subtypes and their clinical significance has been discussed. Present and future methods, governing CRC subtyping in the era of personalized therapy with a special emphasis on CMS subtypes of CRC has been reviewed. Together, discovery and validation of new CRC patient stratification methods, screening for novel therapeutic targets, and enhanced diagnosis of CRC may improve the treatment outcome.

Phytochemicals of Syzygium cumini are used for the treatment of various diseases as a traditional medicine but the mechanism behind their action is not well reported. Antimicrobial activity of methanolic seed extract of S. cumini was done by agar well diffusion assay on Bacillus subtilis and its zone of inhibition was found to be 20.06 mm in comparison to control having no zone of inhibition. MIC of S. cumini was found to be 0.3 mg/ml. Genomic DNA degradation of B. subtilis reveals apoptosis and FE-scanning electron microscope indicates cell wall cracking on several intervals of time. Results of propidium iodide staining showed few bacterial cells were stained in control; however population of stained cells increased after exposing them for varying period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. In silico analysis revealed two components of S. cumini methanolic extract to be active against four enzymes (PDB ID—1W5D, 4OX3, 3MFD and 5E2F) which are crucial for plasma membrane synthesis in B. subtilis. Moreover lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 forming one hydrogen bond each whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F forming four hydrogen bonds and alkyl bonds respectively. It demonstrates that methanolic seed extracts of S. cumini could be used for inhibition of food born infection caused by B. subtilis and also an alternative of prevalent antibiotics.

Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A, and IL1R1). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes CXCL3, IL1B, MET and TNS1 genes (p = 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of TNS1 and MET were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these TNS1 and MET are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.

R-spondins are secretory proteins localized in the endoplasmic reticulum and Golgi bodies and are processed through the secretory pathway. Among the R-spondin family, RSPO2 has emanated as a novel regulator of Wnt signaling, which has now been acknowledged in numerous in vitro and in vivo studies. Cancer is an abnormal growth of cells that proliferates and spreads uncontrollably due to the accumulation of genetic and epigenetic factors that constitutively activate Wnt signaling in various types of cancer. Colorectal cancer (CRC) begins when cells in the colon and rectum follow an indefinite pattern of division due to aberrant Wnt activation as one of the key hallmarks. Decades-long progress in research on R-spondins has demonstrated their oncogenic function in distinct cancer types, particularly CRC. As a critical regulator of the Wnt pathway, it modulates several phenotypes of cells, such as cell proliferation, invasion, migration, and cancer stem cell properties. Recently, RSPO mutations, gene rearrangements, fusions, copy number alterations, and altered gene expression have also been identified in a variety of cancers, including CRC. In this review, we addressed the recent updates regarding the recurrently altered R-spondins with special emphasis on the RSPO2 gene and its involvement in potentiating Wnt signaling in CRC. In addition to the compelling physiological and biological roles in cellular fate and regulation, we propose that RSPO2 would be valuable as a potential biomarker for prognostic, diagnostic, and therapeutic use in CRC.