Two-Part Phase 1 Study to Evaluate the Taste Profile of Novel Belumosudil Oral Suspensions and Assess the Relative Bioavailability and Food Effect of the Selected Belumosudil Oral Suspension Compared With Oral Tablet Reference in Healthy Male Participants.

Belumosudil is a selective rho-associated coiled-coil-containing protein kinase 2 inhibitor in clinical use for the treatment of chronic graft-versus-host disease. The current tablet formulation may be inappropriate for children or adults with dysphagia and/or upper gastrointestinal manifestations of chronic graft-versus-host disease. This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension. Addition of sweetener and/or flavor vehicle improved the taste. Relative bioavailability of 200-mg doses of the oral suspension and tablet in the fed state was similar for belumosudil and its metabolites (KD025m1 and KD025m2), but absorption was faster with the oral suspension (median time to maximum concentration: 2 vs 3 hours). Administration of the oral suspension with food increased exposure compared with fasted administration, with maximum observed concentration being increased by 16% and area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) by 19%. Safety and tolerability were consistent with the known safety profile of belumosudil. These results may support administration of a 200-mg belumosudil oral suspension with or without food.

Evaluation of the drug disposition of RO7049389 with in vitro data and human mass balance supported by physiologically based pharmacokinetic modelling.

AIMS: RO7049389 (linvencorvir) is a developmental oral treatment for chronic hepatitis B virus infection. The aim of this work was to conduct mass balance (MB) and absolute bioavailability (BA) analyses in healthy volunteers, alongside in vitro evaluations of the metabolism of RO7049389 and a major circulating active metabolite M5 in human hepatocytes, and physiologically based pharmacokinetic (PBPK) modelling to refine the underlying drug disposition paradigm. METHODS: Participants in the clinical study (MB: Caucasian, male, n = 6; BA: Caucasian and Asian, male and female, n = 16, 8 in each ethnic groups) received oral [14 C] or unlabelled RO7049389 (600/1000 mg) followed by 100 µg intravenous [13 C]RO7049389. Metabolic pathways with fractions metabolized-obtained from the in vitro incubation results of 10 µM [14 C]RO7049389 and 1 µM M5 with (long-term cocultured) human hepatocytes in the absence and presence of the cytochrome P450 3A4 (CYP3A4) inhibitor itraconazole-were used to complement the PBPK models, alongside the clinical MB and BA data. RESULTS: The model performance in predicting the pharmacokinetic profiles of RO7049389 and M5 aligned with clinical observations in Caucasians and was also successfully applied to Asians. Accordingly, the drug disposition pathways for RO7049389 were postulated with newly characterized estimates of the fractions: biliary excretion by P-glycoprotein (~41%), direct glucuronidation via uridine 5'-diphosphoglucuronosyltransferase 1A3 (~11%), hexose conjugation (~6%), oxidation by CYP3A4 (~28%) and other oxidation reactions (~9%). CONCLUSION: These results support the ongoing clinical development program for RO7049389 and highlight the broader value of PBPK and MB analyses in drug development.

Clinicomycological Profile and Risk Factors for Dermatophytosis at a Teaching Tertiary Care Centre in North India: A Cross-sectional Study.

BACKGROUND: Dermatophytosis has gained significant importance in recent years owing to increased incidence, more atypical lesions, changing mycological profile and growing antifungal resistance. Therefore, this study was planned to know the clinicomycological profile of dermatophytic infections in patients attending our tertiary care centre. MATERIALS AND METHODS: A total of 700 patients with superficial fungal infections belonging to all age groups and both sexes were taken up for this cross-sectional study. Sociodemographic and clinical details were noted on a prestructured proforma. Superficial lesions were clinically examined and the sample was collected by appropriate collection methods. Direct microscopy by potassium hydroxide wet mount was done to see hyphae. For culture Sabouraud's dextrose agar (SDA) with chloramphenicol and cyclohexamide was used. RESULTS: Dermatophytic infections were detected in 75.8% (531/700) patients. Young people belonging to age group of 21-30 years were commonly affected. Tinea corporis was the commonest clinical picture seen in 20% of the cases. Oral antifungals were taken by 33.1% and topical creams were used by 74.2% of the patients. Direct microscopy was positive in 91.3% and culture was positive for dermatophytes in 61% of the study subjects. T. mentagrophytes was the commonest dermatophyte isolated. CONCLUSION: Irrational use of topical steroids needs to be controlled. KOH microscopy can be useful as a point of care test for rapid screening of dermatophytic infections. Culture is necessary to differentiate various dermatophytes and to guide the antifungal treatment.

Agronomic Investigation of Spray Dispersion of Metal-Based Nanoparticles on Sunflowers in Real-World Environments.

In environmental and agronomic settings, even minor imbalances can trigger a range of unpredicted responses. Despite the widespread use of metal-based nanoparticles (NPs) and new bio-nanofertilizers, their impact on crop production is absent in the literature. Therefore, our research is focused on the agronomic effect of spray application of gold nanoparticles anchored to SiO2 mesoporous silica (AuSi-NPs), zinc oxide nanoparticles (ZnO-NPs), and iron oxide nanoparticles (Fe3O4-NPs) on sunflowers under real-world environments. Our findings revealed that the biosynthetically prepared AuSi-NPs and ZnO-NPs were highly effective in enhancing sunflower seasonal physiology, e.g., the value of the NDVI index increased from 0.012 to 0.025 after AuSi-NPs application. The distribution of leaf trichomes improved and the grain yield increased from 2.47 t ha-1 to 3.29 t ha-1 after ZnO-NPs application. AuSi-NPs treatment resulted in a higher content of essential linoleic acid (54.37%) when compared to the NPs-free control (51.57%), which had a higher determined oleic acid. No NPs or residual translocated metals were detected in the fully ripe sunflower seeds, except for slightly higher silica content after the AuSi-NPs treatment. Additionally, AuSi-NPs and NPs-free control showed wide insect biodiversity while ZnO-NPs treatment had the lowest value of phosphorus as anti-nutrient. Contradictory but insignificant effect on physiology, yield, and insect biodiversity was observed in Fe3O4-NPs treatment. Therefore, further studies are needed to fully understand the long-term environmental and agricultural sustainability of NPs applications.

Screening for Multifarious Plant Growth Promoting and Biocontrol Attributes in Bacillus Strains Isolated from Indo Gangetic Soil for Enhancing Growth of Rice Crops.

Multifarious plant growth-promoting Bacillus strains recovered from rhizospheric soils of the Indo Gangetic plains (IGPs) were identified as Bacillus licheniformis MNNITSR2 and Bacillus velezensis MNNITSR18 based on their biochemical characteristics and 16S rDNA gene analysis. Both strains exhibited the ability to produce IAA, siderophores, ammonia, lytic enzymes, HCN production, and phosphate solubilization capability and strongly inhibited the growth of phytopathogens such as Rhizoctonia solani and Fusariun oxysporum in vitro. In addition, these strains are also able to grow at a high temperature of 50 °C and tolerate up to 10-15% NaCl and 25% PEG 6000. The results of the pot experiment showed that individual seed inoculation and the coinoculation of multifarious plant growth promoting (PGP) Bacillus strains (SR2 and SR18) in rice fields significantly enhanced plant height, root length volume, tiller numbers, dry weight, and yield compared to the untreated control. This indicates that these strains are potential candidates for use as PGP inoculants/biofertilizers to increase rice productivity under field conditions for IGPs in Uttar Pradesh, India.

Molecular Weight Controls Interactions between Plastic Deformation and Fracture in Cold Spray of Glassy Polymers.

Polymer cold spray has gained considerable attention as a novel manufacturing process. A promising aspect of this technology involves the ability to deposit uniform polymer coatings without the requirements of solvent and/or high-temperature conditions. The present study investigates the interplay between shear instability, often considered to be the primary mechanism for bond formation, and fracture, as a secondary energy dissipation mechanism, collectively governing the deposition of glassy thermoplastics on similar and dissimilar substrates. A hybrid experimental-computational approach is utilized to explore the simultaneous effects of several interconnected phenomena, namely the particle-substrate relative deformability, molecular weights, and the resultant yielding versus fracture of polystyrene particles, examined herein as a model material system. The computational investigations are based on constitutive plasticity and damage equations determined and calibrated based on a statistical data mining approach applied to a wide collection of previously reported stress-strain and failure data. Results obtained herein demonstrate that the underlying adhesion mechanisms depend strongly on the molecular weight of the sprayed particles. It is also shown that although the plastic deformation and shear instability are still the primary bond formation mechanisms, the molecular-weight-dependent fracture of the sprayed glassy polymers is also a considerable phenomenon capable of significantly affecting the deposition process, especially in cases involving the cold spray of soft thermoplastics on hard substrates. The strong interplay between molecular-weight-dependent plastic yielding and fracture in the examined system emphasizes the importance of molecular weight as a critical variable in the cold spray of glassy polymers, also highlighting the possibility of process optimization by proper feedstock selection.

Improving biofortification success rates and productivity through zinc nanocomposites in rice (Oryza sativa L.).

Rice (Oryza sativa L.) is a staple food crop; most of it is consumed in nations where malnutrition is a serious problem, and its enrichment through biofortification can be used to efficiently combat hidden hunger. Here, we studied the effect of two zinc forms, i.e., zinc oxide nanoparticles (ZnO NPs) and sulfate salt (ZnSO4), at four different concentrations during the grain development period (after anthesis and continued once a week for up to 5 weeks) of the rice plant. During the rice growing season 2021-2022, all the experiments were conducted in a greenhouse (temperature: day 30 °C; night 20 °C; relative humidity: 70%; light period: 16 h/8 h, day/night). The main aim was to identify the effects of ZnO NPs on physical growth, biochemical parameters, nutrient acquisition, and crop yield. We have also highlighted the effects of NPs on zinc biofortification, and the end results illustrated that both zinc forms are capable of increasing grain yield. However, we found that even at low concentrations, ZnO NPs showed a significant increase in growth yield, whereas bulk did not show eminent results even at higher concentrations. Spikelet number per panicle was more than 50% and 38% in the case of ZnO NPs and ZnSO4, respectively. Similarly, stimulation in plant height was 25% with NPs treatment and only 3% with bulk treatment. The increase in grain per spike was 19% with ZnO NPs as compared to the control. Total chlorophyll, soluble sugar, amylose, and soluble protein contents were enhanced under ZnO NP treatment, which plays an excellent role in the regulation of various transcriptional pathways related to biofortification. We identified that foliar application at the flowering stage is more effective in comparison to the basal and tillering stages of the rice life cycle. ZnO NPs increased zinc content in rice grain by 55% as compared to traditional fertilization (~ 35%), with no adverse effects on human health. This study highlights that ZnO NPs could be used to increase zinc efficiency and as a safe fertilizer in the rice harvesting ecosystem.

Sustainable approaches towards green synthesis of TiO2 nanomaterials and their applications in photocatalysis-mediated sensing to monitor environmental pollution.

Nanomaterials are gaining enormous interests due to their novel applications that have been explored nearly in every field of our contemporary society. In this scenario, preparations of nanomaterials following green routes have attracted widespread attention in terms of sustainable, reliable, and environmentally friendly practices to produce diverse nanostructures. In this review, we summarize the fundamental processes and mechanisms of green synthesis approaches of TiO2 nanoparticles (NPs). We explore the role of plants and microbes as natural bioresources to prepare TiO2 NPs. Particularly, focus has been made to explore the potential of TiO2 -based nanomaterials to design a variety of sensing platforms by exploiting the photocatalysis efficiency under the influence of a light source. These types of sensing are of massive importance for monitoring environmental pollution and therefore for inventing advanced strategies to remediate hazardous pollutants and offer a clean environment.

Effect of zinc and iron oxide nanoparticles on plant physiology, seed quality and microbial community structure in a rice-soil-microbial ecosystem.

In this study, we assessed the impact of zinc oxide (ZnO) and iron oxide (FeO) (<36 nm) nanoparticles (NPs) as well as their sulphate salt (bulk) counterpart (0, 25, 100 mg/kg) on rice growth and seed quality as well as the microbial community in the rhizosphere environment of rice. During the rice growing season 2021-22, all experiments were conducted in a greenhouse (temperature: day 30 °C; night 20 °C; relative humidity: 70%; light period: 16 h/8 h, day/night) in rice field soil. Results showed that low concentrations of FeO and ZnO NPs (25 mg/kg) promoted rice growth (height (29%, 16%), pigment content (2%, 3%)) and grain quality parameters such as grains per spike (8%, 9%), dry weight of grains (12%, 14%) respectively. As compared to the control group, the Zn (2%) and Fe (5%) accumulations at their respective low concentrations of NP treatments showed stimulation. Interestingly, our results showed that at low concentration of both the NPs the soil microbes had more diversity and richness than those in the bulk treated and control soil group. Although a number of phyla were affected by the presence of NPs, the strongest effects were observed for change in the abundance of the three phyla for Proteobacteria, Actinobacteria, and Planctomycetes. The rhizosphere environment was notably enriched with potential streptomycin producers, carbon and nitrogen fixers, and lignin degraders with regard to functional groups of microorganisms. However, microbial communities mainly responsible for chitin degradation, ammonia oxidation, and nitrite reduction were found to be decreased. The results from this study highlight significant changes in several plant-based endpoints, as well as the rhizosphere soil microorganisms. It further adds information to our understanding of the nanoscale-specific impacts of important micronutrient oxides on both rice and its associated soil microbiome.

Absorption, metabolism and excretion of opicapone in human healthy volunteers.

AIMS: The absorption, metabolism and excretion of opicapone (2,5-dichloro-3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor, were investigated. METHODS: Plasma, urine and faeces were collected from healthy male subjects following a single oral dose of 100 mg [14 C]-opicapone. The mass balance of [14 C]-opicapone and metabolic profile were evaluated. RESULTS: The recovery of total administered radioactivity averaged >90% after 144 hours. Faeces were the major route of elimination, representing 70% of the administered dose; 5% and 20% were excreted in urine and expired air, respectively. The Cmax of total radioactivity matched that of unchanged opicapone, whereas the total radioactivity remained quantifiable for a longer period, attributed to the contribution of opicapone metabolites, involving primarily 3-O-sulfate conjugation (58.6% of total circulating radioactivity) at the nitrocatechol ring. Other circulating metabolites, accounting for <10% of the radioactivity exposure, were formed by glucuronidation, methylation, N-oxide reduction and gluthatione conjugation. Additionally, various other metabolites resulting from combinations with the opicapone N-oxide reduced form at the 2,5-dichloro-4,6-dimethylpyridine 1-oxide moiety, including nitro reduction and N-acetylation, reductive opening and cleavage of the 1,2,4-oxadiazole ring and the subsequent hydrolysis products were identified, but only in faeces, suggesting the involvement of gut bacteria. CONCLUSION: [14 C]-opicapone was fully excreted through multiple metabolic pathways. The main route of excretion was in faeces, where opicapone may be further metabolized via reductive metabolism involving the 1,2,4-oxadiazole ring-opening and subsequent hydrolysis.

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors.

Belumosudil is a selective Rho-associated protein kinase 2 inhibitor. Inhibition of Rho-associated protein kinase 2 has emerged as a promising treatment for chronic graft-versus-host disease by restoring immune homeostasis and reducing fibrosis. In vitro assessments have suggested that metabolism of belumosudil is primarily dependent on cytochrome P450 (CYP) 3A4 activity and that the solubility of belumosudil is pH dependent. As such, this 2-part clinical drug-drug interaction study was conducted to assess the effect of itraconazole (a strong CYP3A4 inhibitor), rifampicin (a strong CYP3A4 inducer), rabeprazole, and omeprazole (both proton pump inhibitors) on the pharmacokinetics of belumosudil. No clinically relevant change in belumosudil exposure was observed following a 200-mg single oral dose of belumosudil with itraconazole; however, exposure of main metabolite, KD025m2, was decreased. Consistent with the proposed metabolic pathway of belumosudil, the strong CYP3A4 inducer rifampicin significantly decreased exposure of belumosudil and KD025m2 and increased KD025m1 exposure. When a 200-mg single oral dose of belumosudil was coadministered with both rabeprazole and omeprazole, parent and metabolite exposures were largely reduced, suggesting that belumosudil dosage should be increased when given with PPIs. Administration of belumosudil with and without perpetrator drugs was safe, and no notable adverse events were reported.

Absolute Bioavailability, Mass Balance, and Metabolic Profiling Assessment of [14 C]-Belumosudil in Healthy Men: A Phase 1, Open-Label, 2-Part Study.

Belumosudil is a selective Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor. ROCK2 has been shown to drive proinflammatory response and fibrosis that occurs with chronic graft-versus-host disease; therefore, inhibition of ROCK2 has emerged as a therapeutic target for chronic graft-versus-host disease. In this phase 1 two-part study, the pharmacokinetics, mass balance, and metabolic profile of belumosudil were evaluated after single doses of unlabeled belumosudil oral tablets (200 mg), radiolabeled belumosudil intravenous (IV) microtracer infusions (100 µg), and radiolabeled oral capsules (200 mg). Absolute bioavailability based on area under the plasma concentration-time curve from time 0 to infinity for the oral dose/area under the plasma concentration-time curve from time 0 to infinity for the IV dose was calculated as 63.7%. Radiolabeled IV microtracer dosing demonstrated a low extraction ratio and distribution of belumosudil into tissues. The majority of total radioactivity was recovered in feces, with minimal amounts recovered in urine, suggesting minimal renal elimination of belumosudil. In addition to parent and main metabolite KD025m2, metabolites identified in plasma included the phase 2 metabolites O-dealkylated belumosudil sulfate and belumosudil glucuronide. These metabolites (with the exception of the glucuronide) in addition to monohydroxy-belumosudil, and belumosudil diol were identified in feces. No metabolites in urine accounted for >10% of the radioactive dose.

Synergistic action of silicon nanoparticles and indole acetic acid in alleviation of chromium (CrVI) toxicity in Oryza sativa seedlings.

The present study investigates ameliorative effect of silicon nanoparticles (SiNPs) and indole acetic acid (IAA) alone and in combination against hexavalent chromium (CrVI) toxicity in rice seedlings. The results of the study revealed protective effects of SiNPs and IAA against CrVI toxicity. The 100 µM of CrVI imposed toxic effects in rice seedlings at morphological, physiological and biochemical levels which coincided with increased level of intracellular CrVI and declined level of endogenous nitric oxide (NO). The CrVI enhanced levels of superoxide radicals (SOR) (59.51% and 50.1% in shoot and root, respectively) and H2O2 (19.5% and 23.69% in shoot and root, respectively). However, when SiNPs and IAA were applied to plants under CrVI stress, they enhanced tolerance and defence mechanisms as manifested in terms of increased biomass, endogenous NO, photosynthetic pigments, and antioxidants level. It was also noticed that CrVI arrested cell cycle at G2/M phase whereas growth was restored as compared to control when SiNPs and IAA were supplemented. Thus, the hypothesis that combined application of SiNPs and IAA will be effective in alleviating CrVI toxicity is validated from the results of this study. Moreover, in SiNPs and IAA-mediated mitigation of CrVI toxicity, endogenous NO has a positive role. The importance of the study will be that the combination of SiNPs and IAA can be utilized against heavy metal stress and even when supplied alone, they will enhance the crop productivity parameters with and without stress conditions.

Structural analysis of extrafloral nectaries of Senna occidentalis L.: insights on diversity and evolution.

MAIN CONCLUSION: The extrafloral nectaries of S. occidentalis were studied structurally and anatomically (at secretory and post-secretory developmental stages). Role of extrafloral nectaries as a common plant-adoptive characteristic in context to diversity and phylogenetic pattern was also speculated while exploring other collaborative evolutionary implications of this plant. Extrafloral nectaries (EFNs) are widespread and evolutionarily labile traits that have repeatedly and remarkably evolved in vascular plants. Morphological descriptions of the EFNs of certain plant species are common in the literature, but they rarely relate morphology with histology, gland distribution and secretory characteristics. Studies relating EFNs features, i.e., morphology and distribution with their differential visitation by insects, viz. ants and the cost of maintenance to the plants are important to understand the evolution of these glands. Therefore, in this study a morphological, anatomical (structure and ultrastructure) and secretory characterization of EFNs occurring on Senna occidentalis L. is made with the implications of gland attributes discussed from a functional perspective. S. occidentalis L. (Caesalpiniaceae) is an economically important species from industrial, medicinal and agricultural perspective. Observations from the result showed that shape of the EFNs (size 1-2 mm) ranged to globular, ovoid-conical, dome-shaped, fusiform or cylindrical with conical tip. The EFNs were sessile, positioned interpetiolar or seated at the base of petiole. Light and transmission electron microscopic studies showed the specific internal structures of the extrafloral nectary. Two developmental stages of the EFNs (secretory and post-secretory) were recognized. Our current understanding of the phylogenetic patterns of EFNs makes them powerful candidates for future work exploring the drivers of their evolutionary origins, shifts, and losses.

Nanopriming with phytosynthesized zinc oxide nanoparticles for promoting germination and starch metabolism in rice seeds.

The application of zinc oxide nanoparticles (ZnO NPs) in agricultural field is emerging and relatively new. In this work, a simple, cost-efficient, non-toxic and eco-friendly method for the green synthesis of ZnO NPs by Senna occidentalis leaf extract has been described. Techniques used to characterize nanoparticles (NPs) were X-ray diffractometer (XRD), UV visible spectroscopy, Particle size analyzer (PSA), Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). In this study, green synthesized ZnO NPs at 20-40 mg/l solution was used to prime aged seeds of early flowering homozygous mutant (BM6) of Pusa basmati (Oryza sativa), which enhanced germination performance and seedling vigor significantly as compared to zinc sulphate (ZnSO4) priming and conventional hydropriming. The effect of treatment was analyzed by measuring biophysical and biochemical parameter of germinating rice seeds. The seeds treated with ZnO NPs of 20 mg/l concentration showed more than 50 % stimulation in dry weight, relative water uptake of seeds and radicle length of seedling in comparison to other priming solution and control (hydro-primed). Significant growth was also observed in plumule length and fresh weight of seeds in ZnO NPs at 20 mg/l concentration in comparison to control and other priming treatments. At the same concentration of ZnO NPs, there was 23 % stimulation reported in total soluble sugar content and 45 % stimulation in amylase activity. There was also a substantial increase in antioxidant enzymes i.e. superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity. Seed priming represents an innovative user-friendly approach to enhance the germination rate, starch metabolic process and triggered zinc acquisition of rice aged seed as an alternative to the conventional priming method.

Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients.

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.

Molecular subtypes of colorectal cancer: An emerging therapeutic opportunity for personalized medicine.

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.