Liquid Biopsy: A Step Closer to Transform Diagnosis, Prognosis and Future of Cancer Treatments

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes

Tumor Microenvironment: An Evil Nexus Promoting Aggressive Head and Neck Squamous Cell Carcinoma and Avenue for Targeted Therapy

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor-stromal interactions, can lead to new therapeutic interventions in HNSCC. Interestingly, different molecular and immune landscapes between HPV+ve and HPV-ve (human papillomavirus) HNSCC tumors offer new opportunities for developing individualized, targeted chemoimmunotherapy (CIT) regimen. This review highlights the current understanding of the complexity between HPV+ve and HPV-ve HNSCC TME and various tumor-stromal cross-talk modulating processes, including epithelial-mesenchymal transition (EMT), anoikis resistance, angiogenesis, immune surveillance, metastatic niche, therapeutic resistance, and development of an aggressive tumor phenotype. Furthermore, we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV+ve and HPV-ve HNSCC

Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy

Esophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases among patients with advanced disease account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, and growth factors, which play a significant role in supporting the growth and aggressive behavior of cancer cells. The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. The molecular changes in the TME are used as biological markers for diagnosis, prognosis, and response to treatment in patients. This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development. In addition, it discusses the wide range of changes and intracellular signaling pathways that occur in the TME. Overall, this is a relatively unexplored field that could provide crucial insights into tumor immunology and encourage the effective application of modulatory cytokine-chemokine therapy to EC.This study was supported by a PI grant from Sidra Medicine (5071012001) to Mohammad Haris. Ajaz A. Bhat is supported by Sidra Medicine internal grant (5011041002) and Ramalinga swami (Grant number: D.O.NO.BT/HRD/35/02/2006) Fellowship to Muzafar A. Macha and Nissar A. Wani by Department of Biotechnology (DBT), Govt. of India, New Delhi. Shahab Uddin is supported by Medical Research Centre grants (grant# 16102/6, #16354/16)

T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease

In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1ρ) imaging and CSF biomarkers (T-tau, P-tau and Aβ-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1ρ images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1ρ maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1ρ values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1ρ and CSF biomarkers as variables was performed to classify each group. T1ρ was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1ρ and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1ρ predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1ρ and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1ρ predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1ρ were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1ρ showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1ρ and CSF biomarkers, between T1ρ and age, and between CSF biomarkers and age was observed. The combined use of T1ρ and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination

Insights Into the Role of CircRNAs: Biogenesis, Characterization, Functional, and Clinical Impact in Human Malignancies

Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with decreased functionality. However, recent advances in high-throughput genomic technology have allowed circRNAs to be characterized in detail and revealed their role in controlling various biological and molecular processes, the most essential being gene regulation. Because of the structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA biology. Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3′ poly-(A) tail or 5′ cap, rendering them immune to exonuclease-mediated degradation. Emerging research has identified multifaceted roles of circRNAs as miRNA and RNA binding protein (RBP) sponges and transcription, translation, and splicing event regulators. CircRNAs have been involved in many human illnesses, including cancer and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, due to their aberrant expression in different pathological conditions. The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular mechanisms of circRNAs and their use as potential therapeutic targets in different human malignancies