scholarly journals Development of Group B Coxsackievirus as an Oncolytic Virus: Opportunities and Challenges

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1082
Author(s):  
Huitao Liu ◽  
Honglin Luo
Keyword(s):  
Tumor Cells ◽  
Current Knowledge ◽  
Oncolytic Viruses ◽  
Human Enterovirus ◽  
Multiple Cancer ◽  
The Family ◽  
Cancer Types ◽  
Group B ◽  
Type 3 ◽  
Genus Enterovirus

Oncolytic viruses have emerged as a promising strategy for cancer therapy due to their dual ability to selectively infect and lyse tumor cells and to induce systemic anti-tumor immunity. Among various candidate viruses, coxsackievirus group B (CVBs) have attracted increasing attention in recent years. CVBs are a group of small, non-enveloped, single-stranded, positive-sense RNA viruses, belonging to species human Enterovirus B in the genus Enterovirus of the family Picornaviridae. Preclinical studies have demonstrated potent anti-tumor activities for CVBs, particularly type 3, against multiple cancer types, including lung, breast, and colorectal cancer. Various approaches have been proposed or applied to enhance the safety and specificity of CVBs towards tumor cells and to further increase their anti-tumor efficacy. This review summarizes current knowledge and strategies for developing CVBs as oncolytic viruses for cancer virotherapy. The challenges arising from these studies and future prospects are also discussed in this review.

scholarly journals Obesity-Linked Cancers: Current Knowledge, Challenges and Limitations in Mechanistic Studies and Rodent Models

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 523 ◽  
Author(s):  
Yang Xu ◽  
Suresh Mishra
Keyword(s):  
Current Knowledge ◽  
Psychosocial Health ◽  
Rodent Models ◽  
Mechanistic Studies ◽  
Multiple Cancer ◽  
The People ◽  
Incidence And Mortality ◽  
Prevalence Of Obesity ◽  
Clinical Models ◽  
Cancer Types

The worldwide prevalence of obesity has doubled during the last 50 years, and according to the World Obesity Federation, one third of the people on Earth will be obese by the year 2025. Obesity is described as a chronic, relapsing and multifactorial disease that causes metabolic, biomechanical, and psychosocial health consequences. Growing evidence suggests that obesity is a risk factor for multiple cancer types and rivals smoking as the leading preventable cause for cancer incidence and mortality. The epidemic of obesity will likely generate a new wave of obesity-related cancers with high aggressiveness and shortened latency. Observational studies have shown that from cancer risk to disease prognosis, an individual with obesity is consistently ranked worse compared to their lean counterpart. Mechanistic studies identified similar sets of abnormalities under obesity that may lead to cancer development, including ectopic fat storage, altered adipokine profiles, hormone fluctuations and meta-inflammation, but could not explain how these common mechanisms produce over 13 different cancer types. A major hurdle in the mechanistic underpinning of obesity-related cancer is the lack of suitable pre-clinical models that spontaneously develop obesity-linked cancers like humans. Current approaches and animal models fall short when discerning the confounders that often coexist in obesity. In this mini-review, we will briefly survey advances in the different obesity-linked cancers and discuss the challenges and limitations in the rodent models employed to study their relationship. We will also provide our perspectives on the future of obesity-linked cancer research.

scholarly journals AXL is a key factor for cell plasticity and promotes metastasis in pancreatic cancer

2020 ◽  
Author(s):  
Wenting Du ◽  
Huocong Huang ◽  
Zhaoning Wang ◽  
Jason E. Toombs ◽  
Natalie Z. Phinney ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Suppression ◽  
Mesenchymal Tumor ◽  
Ductal Adenocarcinoma ◽  
Nucleoside Transporter ◽  
Cell Plasticity ◽  
Multiple Cancer ◽  
The Us ◽  
Key Factor ◽  
Cancer Types

AbstractPancreatic ductal adenocarcinoma (PDA), a leading cause of cancer-related death in the US, has a high metastatic rate and is associated with persistent immune suppression. AXL, a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family, has been identified as a driver of metastasis and immune suppression in multiple cancer types. Here we use single cell RNA sequencing to reveal that AXL is expressed highly in tumor cells that have a mesenchymal-like phenotype and that AXL expression correlates with classic markers of mesenchymal tumor cells. We demonstrate that AXL-deficiency extends survival, reduces primary and metastatic burden and enhances sensitivity to gemcitabine in an autochthonous model of PDA. PDA in AXL-deficient mice displayed a more differentiated histology, higher nucleoside transporter expression and a more active immune microenvironment compared to PDA in wild-type mice. Finally, we demonstrate that AXL-positive mesenchymal tumor cells are critical for PDA progression and metastasis, emphasizing the potential of AXL as a therapeutic target for PDA patients.

scholarly journals The Paradoxical Behavior of microRNA-211 in Melanomas and Other Human Cancers

2021 ◽  
Vol 10 ◽  
Author(s):  
Animesh Ray ◽  
Haritha Kunhiraman ◽  
Ranjan J. Perera
Keyword(s):  
Tumor Cells ◽  
Multiple Equilibria ◽  
Biological Effects ◽  
Molecular Genetic ◽  
Braf Inhibitor ◽  
Multiple Cancer ◽  
Melanoma Tumor ◽  
Rna Molecules ◽  
Cancer Types

Cancer initiation, progression, and metastasis leverage many regulatory agents, such as signaling molecules, transcription factors, and regulatory RNA molecules. Among these, regulatory non-coding RNAs have emerged as molecules that control multiple cancer types and their pathologic properties. The human microRNA-211 (MIR211) is one such molecule, which affects several cancer types, including melanoma, glioblastoma, lung adenocarcinomas, breast, ovarian, prostate, and colorectal carcinoma. Previous studies suggested that in certain tumors MIR211 acts as a tumor suppressor while in others it behaves as an oncogenic regulator. Here we summarize the known molecular genetic mechanisms that regulate MIR211 gene expression and molecular pathways that are in turn controlled by MIR211 itself. We discuss how cellular and epigenetic contexts modulate the biological effects of MIR211, which exhibit pleiotropic effects. For example, up-regulation of MIR211 expression down-regulates Warburg effect in melanoma tumor cells associated with an inhibition of the growth of human melanoma cells in vitro, and yet these conditions robustly increase tumor growth in xenografted mice. Signaling through the DUSP6-ERK5 pathway is modulated by MIR211 in BRAFV600E driven melanoma tumors, and this function is involved in the resistance of tumor cells to the BRAF inhibitor, Vemurafenib. We discuss several alternate but testable models, involving stochastic cell-to-cell expression heterogeneity due to multiple equilibria involving feedback circuits, intracellular communication, and genetic variation at miRNA target sties, to reconcile the paradoxical effects of MIR211 on tumorigenesis. Understanding the precise role of this miRNA is crucial to understanding the genetic basis of melanoma as well as the other cancer types where this regulatory molecule has important influences. We hope this review will inspire novel directions in this field.

Anticancer Immunotoxins, Challenges, and Approaches

2020 ◽  
Vol 26 ◽  
Author(s):  
Maryam Dashtiahangar ◽  
Leila Rahbarnia ◽  
Safar Farajnia ◽  
Arash Salmaninejad ◽  
Arezoo Gowhari Shabgah ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Antibody Fragment ◽  
Clinical Use ◽  
Multiple Cancer ◽  
Main Obstacle ◽  
Cancer Types ◽  
Recombinant Immunotoxins ◽  
Cancerous Cells ◽  
High Immunogenicity ◽  
Novel Therapeutic

: The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in the treatment of cancer. RITs are resulting from the fusion of antibodies to toxin proteins for targeting and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibiting multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system. This paper devoted to reviewing recent advances in the design of immunotoxins with lower immunogenicity.

Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 1397-1404
Author(s):  
Adrian Bartoszek ◽  
Jakub Fichna ◽  
Aleksandra Tarasiuk ◽  
Agata Binienda ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Current Knowledge ◽  
Developed Countries ◽  
Future Directions ◽  
Screening Programs ◽  
Pharmacological Targets ◽  
The Family ◽  
Free Fatty Acid Receptors

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

Enterovirus D-68 Molecular Virology, Epidemiology, and Treatment: an update and way forward

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud Ahmed Ebada ◽  
Notila Fayed ◽  
Souad Alkanj ◽  
Ahmed Wadaa Allah
Keyword(s):  
Current Knowledge ◽  
Rna Virus ◽  
Neurological Diseases ◽  
Cross Reactivity ◽  
Serological Tests ◽  
Molecular Virology ◽  
Acute Flaccid Myelitis ◽  
The Family ◽  
Pcr Products ◽  
Enterovirus D68

: Enterovirus D68 (EV-D68) is a single-stranded positive-sense RNA virus, and it is one of the family Picornaviridae. Except for EV-D68, the family Picornaviridae has been illustrated in literature. EV-D68 was first discovered and isolated in California, USA, in 1962. EV-D68 has resulted in respiratory disorders’ outbreaks among children worldwide, and it has been detected in cases of various neurological diseases such as acute flaccid myelitis (AFM). A recent study documented a higher number of EV-D68 cases associated with AFM in Europe in 2016 compared to the 2014 outbreak. EV-D68 is mainly diagnosed by quantitative PCR, and there is an affirmative strategy for EV-D68 detection by using pan-EV PCR on the untranslated region and/or the VP1 or VP2, followed by sequencing of the PCR products. Serological tests are limited due to cross-reactivity of the antigens between the different serotypes. Many antiviral drugs for EV-D68 have been evaluated, and showed promising results. In our review, we discuss the current knowledge about EV-D68 and its role in the development of AFM.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3386
Author(s):  
Bart Spiesschaert ◽  
Katharina Angerer ◽  
John Park ◽  
Guido Wollmann
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Cells ◽  
Small Molecule ◽  
Antiviral Immunity ◽  
Oncolytic Viruses ◽  
Antitumor Immune Response ◽  
Antiviral Responses ◽  
Small Molecule Therapeutics ◽  
Immunosuppressive Factors

The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

scholarly journals Landscape of Chimeric RNAs in Non-Cancerous Cells

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 466
Author(s):  
Chen Chen ◽  
Samuel Haddox ◽  
Yue Tang ◽  
Fujun Qin ◽  
Hui Li
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Drug Targets ◽  
Neoplastic Cell ◽  
Multiple Cancer ◽  
Chimeric Rnas ◽  
Healthy Donors ◽  
Cancer Types ◽  
Chimeric Rna ◽  
Cancerous Cells

Gene fusions and their products (RNA and protein) have been traditionally recognized as unique features of cancer cells and are used as ideal biomarkers and drug targets for multiple cancer types. However, recent studies have demonstrated that chimeric RNAs generated by intergenic alternative splicing can also be found in normal cells and tissues. In this study, we aim to identify chimeric RNAs in different non-neoplastic cell lines and investigate the landscape and expression of these novel candidate chimeric RNAs. To do so, we used HEK-293T, HUVEC, and LO2 cell lines as models, performed paired-end RNA sequencing, and conducted analyses for chimeric RNA profiles. Several filtering criteria were applied, and the landscape of chimeric RNAs was characterized at multiple levels and from various angles. Further, we experimentally validated 17 chimeric RNAs from different classifications. Finally, we examined a number of validated chimeric RNAs in different cancer and non-cancer cells, including blood from healthy donors, and demonstrated their ubiquitous expression pattern.

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