scholarly journals lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2148 ◽  
Author(s):  
Dominik A. Barth ◽  
Jaroslav Juracek ◽  
Ondrej Slaby ◽  
Martin Pichler ◽  
George A. Calin
Keyword(s):  
Drug Resistance ◽  
Treatment Options ◽  
Cancer Therapies ◽  
Protein Coding ◽  
Genitourinary System ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Novel Therapeutic Strategies ◽  
Regulatory Functions

Available systemic treatment options for cancers of the genitourinary system have experienced great progress in the last decade. However, a large proportion of patients eventually develop resistance to treatment, resulting in disease progression and shorter overall survival. Biomarkers indicating the increasing resistance to cancer therapies are yet to enter clinical routine. Long non-coding RNAs (lncRNA) are non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types of regulatory functions of all known cellular processes. Increasing evidence supports the role of lncRNAs in cancer development and progression. Additionally, their involvement in the development of drug resistance across various cancer entities, including genitourinary malignancies, are starting to be discovered. Consequently, lncRNAs have been suggested as factors in novel therapeutic strategies to overcome drug resistance in cancer. In this review, the existing evidences on lncRNAs and their involvement in mechanisms of drug resistance in cancers of the genitourinary system, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, will be highlighted and discussed to facilitate and encourage further research in this field. We summarize a significant number of lncRNAs with proposed pathways in drug resistance and available reported studies.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals The Role of N6-Methyladenosine (m6A) Methylation Modifications in Hematological Malignancies

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 332
Author(s):  
Yan Zhao ◽  
Hongling Peng
Keyword(s):  
Bone Marrow ◽  
Pluripotent Stem Cells ◽  
Rna Splicing ◽  
Messenger Rna ◽  
Hematologic Malignancies ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
Regulatory Functions ◽  
Increased Susceptibility

Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m6A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m6A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents. Therefore, this review elaborates on the biological characteristics and normal hematopoietic regulatory functions of m6A methylation modifications and their role in the pathogenesis of hematologic malignancies.

scholarly journals The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ling Wei ◽  
Xingwu Wang ◽  
Liyan Lv ◽  
Jibing Liu ◽  
Huaixin Xing ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Multiple Tumor ◽  
Nucleolar Rnas

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.

Signal transducer and activator of transcription proteins in leukemias

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 2940-2954 ◽  
Author(s):  
Mustafa Benekli ◽  
Maria R. Baer ◽  
Heinz Baumann ◽  
Meir Wetzler
Keyword(s):  
Potential Role ◽  
Cellular Transformation ◽  
Leukemia Cells ◽  
Signal Transducer ◽  
Stat Proteins ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
Stat Signaling ◽  
Novel Therapeutic Strategies

Abstract Signal transducer and activator of transcription (STAT) proteins are a 7-member family of cytoplasmic transcription factors that contribute to signal transduction by cytokines, hormones, and growth factors. STAT proteins control fundamental cellular processes, including survival, proliferation, and differentiation. Given the critical roles of STAT proteins, it was hypothesized that inappropriate or aberrant activation of STATs might contribute to cellular transformation and, in particular, leukemogenesis. Constitutive activation of mutated STAT3 has in fact been demonstrated to result in transformation. STAT activation has been extensively studied in leukemias, and mechanisms of STAT activation and the potential role of STAT signaling in leukemogenesis are the focus of this review. A better understanding of mechanisms of dysregulation of STAT signaling pathways may serve as a basis for designing novel therapeutic strategies that target these pathways in leukemia cells.

scholarly journals Emerging Role of E2F Family in Cancer Stem Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Dan Xie ◽  
Qin Pei ◽  
Jingyuan Li ◽  
Xue Wan ◽  
Ting Ye
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Tumor Development ◽  
Transcriptional Repressors ◽  
Cellular Processes ◽  
Damage Response ◽  
Prevent Tumor Growth ◽  
Cycle Regulation

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.

scholarly journals Evolutionary Patterns of Non-Coding RNA in Cardiovascular Biology

2019 ◽  
Vol 5 (1) ◽  
pp. 15 ◽  
Author(s):  
Shrey Gandhi ◽  
Frank Ruehle ◽  
Monika Stoll
Keyword(s):  
Vascular System ◽  
Functional Characterization ◽  
Evolutionary Patterns ◽  
Protein Coding ◽  
Rna Transcripts ◽  
Non Coding Rna ◽  
High Prevalence ◽  
Cardiovascular Biology ◽  
Non Coding Rnas

Cardiovascular diseases (CVDs) affect the heart and the vascular system with a high prevalence and place a huge burden on society as well as the healthcare system. These complex diseases are often the result of multiple genetic and environmental risk factors and pose a great challenge to understanding their etiology and consequences. With the advent of next generation sequencing, many non-coding RNA transcripts, especially long non-coding RNAs (lncRNAs), have been linked to the pathogenesis of CVD. Despite increasing evidence, the proper functional characterization of most of these molecules is still lacking. The exploration of conservation of sequences across related species has been used to functionally annotate protein coding genes. In contrast, the rapid evolutionary turnover and weak sequence conservation of lncRNAs make it difficult to characterize functional homologs for these sequences. Recent studies have tried to explore other dimensions of interspecies conservation to elucidate the functional role of these novel transcripts. In this review, we summarize various methodologies adopted to explore the evolutionary conservation of cardiovascular non-coding RNAs at sequence, secondary structure, syntenic, and expression level.

Non-coding RNAs in Lung Cancer Chemoresistance

2020 ◽  
Vol 20 (13) ◽  
pp. 1023-1032 ◽  
Author(s):  
Priya Mondal ◽  
Jagadish Natesh ◽  
Mohammad Amjad Kamal ◽  
Syed Musthapa Meeran
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Gene Expressions ◽  
Intrinsic Factors ◽  
Non Coding Rnas ◽  
Altered Gene

Background: Lung cancer is the leading cause of cancer-associated death worldwide with limited treatment options. The major available treatment options are surgery, radiotherapy, chemotherapy and combinations of these treatments. In chemotherapy, tyrosine kinase inhibitors and taxol are the first lines of chemotherapeutics used for the treatment of lung cancer. Often drug resistance in the clinical settings hinders the efficiency of the treatment and intrigues the tumor relapse. Drug-resistance is triggered either by intrinsic factors or due to the prolonged cycles of chemotherapy as an acquired-resistance. There is an emerging role of non-coding RNAs (ncRNAs), including notorious microRNAs (miRNAs), proposed to be actively involved in the regulations of various tumor-suppressor genes and oncogenes. Result: The altered gene expression by miRNA is largely mediated either by the degradation or by interfering with the translation of targeted mRNA. Unlike miRNA, other type of ncRNAs, such as long non-coding RNAs (lncRNAs), can target the transcriptional activator or the repressor, RNA polymerase, and even DNA-duplex to regulate the gene expressions. Many studies have confirmed the crucial role of ncRNAs in lung adenocarcinoma progression and importantly, in the acquisition of chemoresistance. Recently, ncRNAs have become early biomarkers and therapeutic targets for lung cancer. Conclusion: Targeting ncRNAs could be an effective approach for the development of novel therapeutics against lung cancer and to overcome the chemoresistance.

Non-coding RNA-Encoded Peptides/Proteins in Human Cancer: The Future for Cancer Therapy

2021 ◽  
Vol 28 ◽  
Author(s):  
Seyedeh Zahra Bakhti ◽  
Saeid Latifi-Navid
Keyword(s):  
Cancer Metabolism ◽  
Human Cancer ◽  
Open Reading Frames ◽  
Clinical Value ◽  
Rna Transcripts ◽  
Non Coding Rna ◽  
Present Information ◽  
Regulatory Functions ◽  
Potential Use

: Although non-coding RNAs (ncRNAs) were initially thought to be a class of RNA transcripts with no encoding capability, it has been established that some ncRNAs actually contain open reading frames (ORFs), which can be translated into micropeptides or microproteins. Recent studies have reported that ncRNAs-derived micropeptides/microproteins have regulatory functions on various biological and oncological processes. Some of these micropeptides/microproteins act as tumor inhibitors and some as tumor inducers. Understanding the carcinogenic role of ncRNAs-encoded micropeptides/microproteins seems to pose potential challenges to cancer research and offer promising practical perspectives on cancer treatment. In this review, we summarized the present information on the association of ncRNAs-derived micropeptides/microproteins with different types of human cancers. We also mentioned their carcinogenic mechanisms in cancer metabolism, signaling pathways, cell proliferation, angiogenesis, metastasis, and so on. Finally, we discussed the potential clinical value of these micropeptides/microproteins and their potential use in the diagnosis and treatment of cancer. This information may help discover, optimize, and develop new tools based on biological micropeptides/microproteins for the early diagnosis and development of anticancer drugs.

scholarly journals Therapeutic Approaches and Role of ncRNAs in Cardiovascular Disorders and Insulin Resistance

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Kalupahana Irushi Pamodya Liyanage ◽  
Gamage Upeksha Ganegoda
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Cardiovascular Diseases ◽  
Gene Expression Regulation ◽  
Therapeutic Approaches ◽  
Gene Expressions ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Regulatory Functions

Diseases resulting from alterations in gene expressions through mutations in the genes or through changes in the gene expression regulation could be identified through the analysis of RNA expressions. ncRNAs play a significant role in regulation of the gene expression by controlling the expression levels of the coding RNAs and other cellular processes. Discoveries have shown that the human genome is encoded with sequences responsible for the transcription of thousands of ncRNAs. Even though the studies conducted on ncRNAs are still at initial stages, facts established so far display biomarkers that confirm their relationship with certain diseases such as cancers, cardiovascular diseases, and insulin resistance. These studies have been facilitated with high throughput modern sequencing techniques such as microarrays and RNA sequencing. The data obtained through the above analysis are processed with the aid of existing databases, to deduce conclusions on different diagnostic biomarkers and therapeutic targets for specific diseases. This review focuses on the association of ncRNAs in disease prediction, focusing mainly on cardiovascular diseases and disorders caused by insulin resistance. The report also analyzes regulatory functions of ncRNAs and novel approaches used in disease therapeutics.

scholarly journals Adjusting the Molecular Clock: The Importance of Circadian Rhythms in the Development of Glioblastomas and Its Intervention as a Therapeutic Strategy

2021 ◽  
Vol 22 (15) ◽  
pp. 8289
Author(s):  
Paula M. Wagner ◽  
César G. Prucca ◽  
Beatriz L. Caputto ◽  
Mario E. Guido
Keyword(s):  
Circadian Clock ◽  
World Health ◽  
Novel Treatments ◽  
Cellular Processes ◽  
Circadian Timing System ◽  
The Central Nervous System ◽  
Health Organization ◽  
Novel Therapeutic Strategies ◽  
And Behavior

Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells. The potentiality of the function of the circadian clock on cancer cells modulation as a new target for novel treatments with a chronobiological basis offers a different challenge that needs to be considered in further detail. The present review will discuss state of the art regarding GBM biology, the role of the circadian clock in tumor progression, and new chrono-chemotherapeutic strategies applied for GBM treatment.

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