A Comprehensive Review of Bioinformatics Tools for Genomic Biomarker Discovery Driving Precision Oncology.

The rapid advancement of high-throughput technologies, particularly next-generation sequencing (NGS), has revolutionized cancer research by enabling the investigation of genetic variations such as SNPs, copy number variations, gene expression, and protein levels. These technologies have elevated the significance of precision oncology, creating a demand for biomarker identification and validation. This review explores the complex interplay of oncology, cancer biology, and bioinformatics tools, highlighting the challenges in statistical learning, experimental validation, data processing, and quality control that underpin this transformative field.

Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is the second most common cause of cancer death in American men. Metastatic castration-resistant prostate cancer (mCRPC) is the most lethal form of PCa and preferentially metastasizes to the bones through incompletely understood molecular mechanisms. Herein, we processed RNA sequencing data from patients with mCRPC ( = 60) and identified 14 gene clusters (modules) highly correlated with mCRPC bone metastasis.

Increasing Clinical Trial Participation of Black Women Diagnosed with Breast Cancer.

Despite racial disparities in breast cancer mortality, Black women remain underrepresented in clinical trials. In this mixed methods research, 48 Black women were engaged via focus group discussions and in-depth interviews to better understand the lived experience of women with breast cancer. The results of this qualitative study informed the development of a subsequent online survey to identify barriers, motivators, and other factors that influence decision-making by Black women diagnosed with breast cancer when considering clinical trial participation.

Racial disparities in Black men with prostate cancer: A literature review.

Black men are disproportionately affected by prostate cancer (PCa), with earlier presentation, more aggressive disease, and higher mortality rates versus White men. Furthermore, Black men have less access to PCa treatment and experience longer delays between diagnosis and treatment. In this review, the authors discuss the factors contributing to racial disparities and present solutions to improve access to care and increase clinical trial participation among Black men with PCa.

Multivariant Transcriptome Analysis Identifies Modules and Hub Genes Associated with Poor Outcomes in Newly Diagnosed Multiple Myeloma Patients.

The molecular mechanisms underlying chemoresistance in some newly diagnosed multiple myeloma (MM) patients receiving standard therapies (lenalidomide, bortezomib, and dexamethasone) are poorly understood. Identifying clinically relevant gene networks associated with death due to MM may uncover novel mechanisms, drug targets, and prognostic biomarkers to improve the treatment of the disease. This study used data from the MMRF CoMMpass RNA-seq dataset (N = 270) for weighted gene co-expression network analysis (WGCNA), which identified 21 modules of co-expressed genes.

Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets.

Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered.

Identification of Gene Co-Expression Networks Associated with Consensus Molecular Subtype-1 of Colorectal Cancer.

Colorectal cancer (CRC) is driven in part by dysregulated Wnt, Ras-Raf-MAPK, TGF-β, and PI3K-Akt signaling. The progression of CRC is also promoted by molecular alterations and heterogeneous-yet interconnected-gene mutations, chromosomal instability, transcriptomic subtypes, and immune signatures. Genomic alterations of CRC progression lead to changes in RNA expression, which support CRC metastasis.

RPPA-based proteomics recognizes distinct epigenetic signatures in chronic lymphocytic leukemia with clinical consequences.

The chronic lymphocytic leukemia (CLL) armamentarium has evolved significantly, with novel therapies that inhibit Bruton Tyrosine Kinase, PI3K delta and/or the BCL2 protein improving outcomes. Still, the clinical course of CLL patients is highly variable and most previously recognized prognostic features lack the capacity to predict response to modern treatments indicating the need for new prognostic markers. In this study, we identified four epigenetically distinct proteomic signatures of a large cohort of CLL and related diseases derived samples (n = 871) using reverse phase protein array technology.

Multivariate transcriptome analysis identifies networks and key drivers of chronic lymphocytic leukemia relapse risk and patient survival.

Background: Chronic lymphocytic leukemia (CLL) is an indolent heme malignancy characterized by the accumulation of CD5 CD19 B cells and episodes of relapse. The biological signaling that influence episodes of relapse in CLL are not fully described. Here, we identify gene networks associated with CLL relapse and survival risk.

A network approach reveals driver genes associated with survival of patients with triple-negative breast cancer.

We aimed to identify triple-negative breast cancer (TNBC) drivers that regulate survival time as predictive signatures that improve TNBC prognostication. Breast cancer (BrCa) transcriptomic tumor biopsies were analyzed, identifying network communities enriched with TNBC-specific differentially expressed genes (DEGs) and correlated strongly to TNBC status. Two anticorrelated modules correlated strongly to TNBC subtype and survival.

Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer.

An abnormality in hedgehog (Hh) signaling has been implicated in the progression of prostate cancer (PCa) to a more aggressive and therapy-resistant disease. Our assessments of human PCa tissues have shown an overexpression of the Hh pathway molecules, glioma-associated oncogene homolog 1 (GLI-1), and sonic hedgehog (SHH). The effect of the natural compound thymoquinone (TQ) in controlling the expression of Hh signaling molecules in PCa was investigated in this study.

Role of natural compounds in preventing and treating breast cancer.

Breast cancer (BrCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related death in women. Alarming increases in the cases quests for more effective treatment of BrCa. As most chemotherapeutic drugs are associated with drug resistance, cancer relapse, and side effects, scientists are turning to agents with more efficacy, such as natural compounds for treatment and prevention of BrCa.

Transcriptome Network Analysis Identifies CXCL13-CXCR5 Signaling Modules in the Prostate Tumor Immune Microenvironment.

The tumor immune microenvironment (TIME) consists of multiple cell types that contribute to the heterogeneity and complexity of prostate cancer (PCa). In this study, we sought to understand the gene-expression signature of patients with primary prostate tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular "disease-free months" and "disease reoccurrence". We tested the hypothesis that the CXCL13-CXCR5 axis is co-expressed with factors supporting TIME and PCa progression.

SMR peptide antagonizes mortalin promoted release of extracellular vesicles and affects mortalin protection from complement-dependent cytotoxicity in breast cancer cells and leukemia cells.

Mortalin/GRP-75/mt-hsp70 is a mitochondrial chaperone protein, found in the cytoplasm, endoplasmic reticulum and cytoplasmic vesicles. It functions in many cellular processes such as mitochondrial biogenesis, intracellular trafficking, cell proliferation, signaling, immortalization and tumorigenesis. Thus, inhibition of mortalin is a promising avenue for cancer therapy.

Prostate cancer cells hyper-activate CXCR6 signaling by cleaving CXCL16 to overcome effect of docetaxel.

Molecular reprogramming in response to chemotherapeutics leads to poor therapeutic outcomes for prostate cancer (PCa). In this study, we demonstrated that CXCR6-CXCL16 axis promotes DTX resistance and acts as a counter-defense mechanism. After CXCR6 activation, cell death in response to DTX was inhibited, and blocking of CXCR6 potentiated DTX cytotoxicity.

Higher CXCL16 exodomain is associated with aggressive ovarian cancer and promotes the disease by CXCR6 activation and MMP modulation.

Ovarian cancer (OvCa) is the leading cause of death from gynecological malignancies. Five-year survival rate of OvCa ranges from 30-92%, depending on the spread of disease at diagnosis. Role of chemokines is well appreciated in cancer, including OvCa.

Reversal of drug resistance by planetary ball milled (PBM) nanoparticle loaded with resveratrol and docetaxel in prostate cancer.

The folate receptor (FR) is a valued target that is highly expressed in various cancers, which will expedite the development of ligand-receptor binding based cancer therapeutics. In the present investigation, through tissue microarray analysis, we report higher levels of folate receptor expression in prostate cancer (PCa) tissue derived from patients, which were minimal in normal tissue. For folate-receptor based targeted therapy of PCa, we generated novel planetary ball milled (PBM) nanoparticles (NPs) encapsulated with resveratrol (RES), and in combination with docetaxel (DTX) and conjugated with folic acid (FA) on the surface.

CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells.

Pancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is not known.

Drug delivery approaches for breast cancer.

Breast cancer is one of the most common cancers affecting women worldwide. The controlled release of drugs to the precise site of the disease using a nanocarrier vehicle increases the therapeutic efficiency of the drugs. Nanotechnology-based approaches used to endorse clinical improvement from a disease also help to understand the interaction of malignant cells with their microenvironment.

Calibrated flux measurements reveal a nanostructure-stimulated transcytotic pathway.

Transport of therapeutic agents across epithelial barriers is an important element in drug delivery. Transepithelial flux is widely used as a measure of transit across an epithelium, however it is most typically employed as a relative as opposed to absolute measure of molecular movement. Here, we have used the calcium switch approach to measure the maximum rate of paracellular flux through unencumbered intercellular junctions as a method to calibrate the flux rates for a series of tracers ranging in 0.

Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/ p21WAF1/CIP1 and p27KIP1 pathway.

Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression.

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer.

Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential.