Personalized medicine and new therapeutic approach in the treatment of pancreatic cancer

Pancreatic cancer (PC) is the seventh most common cause of death with a poor prognosis. Although there are many advanced therapeutic approaches, the 5-year survival rate of PC is approximately 11%, so it is one of the most aggressive cancers. The absence of potential biomarkers for early detection and screening is the main reason for poor prognosis and chemoresistance. Personalized medicine (PM) is an emerging approach using the characteristics and differences of patients in the molecular, physiological, environmental, and behavioral fields for better decision-making. In addition, novel quantitative imaging methods, including radiomic and deep learning, make a new noninvasive PM for a better early diagnosis and treatment of PC. However, PM encounters challenges that should be addressed that slow down its worldwide development, including ethical issues and relatively high costs. Here we summarize the novel therapeutic approaches and emerging research models, including patient derived xenograft (PDX) and 3-dimensional organoids, based on the patient’s tumor profile, which provides a better understanding of tumor and TME behavior and its response to drugs.</p

Prognostic value of primary tumor location in colorectal cancer: an updated meta-analysis

The clinical, histological, and molecular differences between right-sided colon cancer (RCC) and left-sided colon cancer (RCC) have received considerable attention. Over the past decade, many articles have been published concerning the association between primary tumor location (PTL) of colorectal cancer and survival outcomes. Therefore, there is a growing need for an updated meta-analysis integrating the outcomes of recent studies to determine the prognostic role of right vs left-sidedness of PTL in patients with colorectal cancer. We conducted a comprehensive database review using PubMed, SCOPUS, and Cochrane library databases from February 2016 to March 2023 for prospective or retrospective studies reporting data on overall survival (OS) and cancer-specific survival (CSS) of RCC compared with LCC. A total of 60 cohort studies comprising 1,494,445 patients were included in the meta-analysis. We demonstrated that RCC is associated with a significantly increased risk of death compared with LCC by 25% (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.19–1.31; I2 = 78.4%; Z = 43.68). Results showed that patients with RCC have a worse OS compared with LCC only in advanced stages (Stage III: HR, 1.275; 95% CI 1.16–1.4; P = 0.0002; I2 = 85.8%; Stage IV: HR, 1.34; 95% CI 1.25–1.44; P < 0.0001; I2 = 69.2%) but not in primary stages (Stage I/II: HR, 1.275; 95% CI 1.16–1.4; P = 0.0002; I2 = 85.8%). Moreover, a meta-analysis of 13 studies including 812,644 patients revealed that there is no significant difference in CSS between RCC and LCC (HR, 1.121; 95% CI 0.97–1.3; P = 0.112). Findings from the present meta-analysis highlight the importance of PTL in clinical decision-making for patients with CRC, especially in advanced stages. We provide further evidence supporting the hypothesis that RCC and LCC are distinct disease entities that should be managed differently.</p

Association of the 1236C >T variant of the multidrug resistance 1 gene with esophageal squamous cell carcinoma development and prognosis

Background: Esophageal squamous cell carcinoma (ESCC) is a common cause of cancer related mortality. There is a growing body of evidence showing an association between genetic variants in the 7q21.12 gene locus and an increased risk of cancer. Here we have explored the association between the 1236C >T; rs1128503 genetic variant of the ABCB1/MDR1 gene with the development and prognosis of ESCC. Method: Data from the computer-based patient records (CPRs) of 10 years (between 2005-2014) of the Mashhad University of Medical Sciences were used to identify patients with ESCC. Ninety-three ESCC patients and two hundred and twenty-four healthy subjects were recruited. DNA was extracted and genotyped using a Taq-Man based real-time PCR method. The association of the variant with overall-survival (OS) and progression-free survival (PFS) was analyzed using Kaplan–Meier curves, log-rank tests, and Cox model. Results: Patients with ESCC had a higher frequency of the C allele compared to the control group with Minor allele frequency (MAF) of 1.5. Moreover, 22%, and 56% of cases had TT and TC genotypes, compared to 22% for CC. Patients with TT genotype, versus CC had a higher risk of ESCC (OR: 2.3; 95%CI: 1.08-4.8, P= 0.03), although it was not associated with PFS and OS (e.g., OS of TT genotype: 56.8±6.9 months versus OS of CC genotype: 60.5±5.7 59 months). Conclusion Our data showed a relationship between a genetic polymorphism of the ABCB1 gene with clinical outcomes of the ESCC-patients, supporting further studies in a larger, and multi-centre settings followed by functional assays to assess the prognostic value of this emerging marker in esophageal squamous cell carcinoma patients

Role of gut bacterial and non-bacterial microbiota in alcohol-associated liver disease: Molecular mechanisms, biomarkers and therapeutic prospective

Alcohol-associated liver disease (ALD) comprises a spectrum of liver diseases that include: steatosis to alcohol-associated hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The pathophysiology and potential underlying mechanisms for alcohol-associated liver disease are unclear. Moreover, the treatment of ALD remains a challenge. Intestinal microbiota include bacteria, fungi, and viruses, that are now known to be important in the development of ALD. Alcohol consumption can change the gut microbiota and function leading to liver disease. Given the importance of interactions between intestinal microbiota, alcohol, and liver injury, the gut microbiota has emerged as a potential biomarker and therapeutic target. This review focuses on the potential mechanisms by which the gut microbiota may be involved in the pathogenesis of ALD and explains how this can be translated into clinical management. We discuss the potential of utilizing the gut microbiota signature as a biomarker in ALD patients. Additionally, we present an overview of the prospect of modulating the intestinal microbiota for the management of ALD

Preclinical tumor mouse models for studying esophageal cancer

Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer. In this review, we have elucidated the production and usage of current mouse models, such as xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), for studying esophageal cancer. Additionally, we have briefly discussed various gene-editing tools that could potentially be employed in the future to create mouse models specifically for esophageal cancer research.</p

Bioinformatics analysis and machine learning approach applied to the identification of novel key genes involved in non-alcoholic fatty liver disease

Abstract Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver

The potential therapeutic applications of CRISPR/Cas9 in colorectal cancer

The application of the CRISPR-associated nuclease 9 (Cas9) system in tumor studies has led to the discovery of several new treatment strategies for colorectal cancer (CRC), including the recognition of novel target genes, the construction of animal mass models, and the identification of genes related to chemotherapy resistance. CRISPR/Cas9 can be applied to genome therapy for CRC, particularly regarding molecular-targeted medicines and suppressors. This review summarizes some aspects of using CRISPR/Cas9 in treating CRC. Further in-depth and systematic research is required to fully realize the potential of CRISPR/Cas9 in CRC treatment and integrate it into clinical practice

The potential therapeutic applications of CRISPR/Cas9 in colorectal cancer

The application of the CRISPR-associated nuclease 9 (Cas9) system in tumor studies has led to the discovery of several new treatment strategies for colorectal cancer (CRC), including the recognition of novel target genes, the construction of animal mass models, and the identification of genes related to chemotherapy resistance. CRISPR/Cas9 can be applied to genome therapy for CRC, particularly regarding molecular-targeted medicines and suppressors. This review summarizes some aspects of using CRISPR/Cas9 in treating CRC. Further in-depth and systematic research is required to fully realize the potential of CRISPR/Cas9 in CRC treatment and integrate it into clinical practice

The therapeutic potential value of Cancer-testis antigens in immunotherapy of gastric cancer

Gastric cancer (GC) is the fourth most common cause of mortality and the fifth for incidence, globally. Diagnosis, early prognosis, and therapy remains challenging for this condition, and new tumor-associated antigens are required for its detection and immunotherapy. Cancer-testis antigens (CTAs) are a subfamily of tumor-associated antigens (TAAs) that have been identified as potential biomarkers and targets for cancer immunotherapy. The CTAs-restricted expression pattern in tumor cells and their potential immunogenicity identify them as attractive target candidates in CTA-based diagnosis or prognosis or immunotherapy. To date, numerous studies have reported the dysregulation of CTAs in GC. Several clinical trials have been done to assess CTA-based immunotherapeutic potential in the treatment of GC patients. NY-ESO-1, MAGE, and KK-LC-1 have been used in GC clinical trials. We review recent studies that have investigated the potential of the CTAs in GC regarding the expression, function, aggressive phenotype, prognosis, and immunological responses as well as their possible clinical significance as immunotherapeutic targets with a focus on challenges and future interventions