scholarly journals Chromatin insulation dynamics in glioblastoma: challenges and future perspectives of precision oncology

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Borja Sesé ◽  
Miquel Ensenyat-Mendez ◽  
Sandra Iñiguez ◽  
Pere Llinàs-Arias ◽  
Diego M. Marzese
Keyword(s):  
Stem Cells ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Small Population ◽  
Precision Oncology ◽  
Loop Formation ◽  
Therapeutic Approaches ◽  
Dna Hypermethylation ◽  
Dna Loop

AbstractGlioblastoma (GBM) is the most aggressive primary brain tumor, having a poor prognosis and a median overall survival of less than two years. Over the last decade, numerous findings regarding the distinct molecular and genetic profiles of GBM have led to the emergence of several therapeutic approaches. Unfortunately, none of them has proven to be effective against GBM progression and recurrence. Epigenetic mechanisms underlying GBM tumor biology, including histone modifications, DNA methylation, and chromatin architecture, have become an attractive target for novel drug discovery strategies. Alterations on chromatin insulator elements (IEs) might lead to aberrant chromatin remodeling via DNA loop formation, causing oncogene reactivation in several types of cancer, including GBM. Importantly, it is shown that mutations affecting the isocitrate dehydrogenase (IDH) 1 and 2 genes, one of the most frequent genetic alterations in gliomas, lead to genome-wide DNA hypermethylation and the consequent IE dysfunction. The relevance of IEs has also been observed in a small population of cancer stem cells known as glioma stem cells (GSCs), which are thought to participate in GBM tumor initiation and drug resistance. Recent studies revealed that epigenomic alterations, specifically chromatin insulation and DNA loop formation, play a crucial role in establishing and maintaining the GSC transcriptional program. This review focuses on the relevance of IEs in GBM biology and their implementation as a potential theranostic target to stratify GBM patients and develop novel therapeutic approaches. We will also discuss the state-of-the-art emerging technologies using big data analysis and how they will settle the bases on future diagnosis and treatment strategies in GBM patients.

scholarly journals Targeting cancer stem cells in squamous cell carcinoma

2019 ◽  
Vol 2 (3) ◽  
pp. 152-165 ◽  
Author(s):  
Demeng Chen ◽  
Cun-Yu Wang
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Strategies ◽  
Cell Types ◽  
Current Treatment ◽  
Small Population

AbstractHead and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor and the sixth most common cancer worldwide. Current treatment strategies for HNSCC are surgery, radiotherapy, chemotherapy, immunotherapy or combinatorial therapies. However, the overall 5-year survival rate of HNSCC patients remains at about 50%. Cancer stem cells (CSCs), a small population among tumor cells, are able to self-renew and differentiate into different tumor cell types in a hierarchical manner, similar to normal tissue. In HNSCC, CSCs are proposed to be responsible for tumor initiation, progression, metastasis, drug resistance, and recurrence. In this review, we discuss the molecular and cellular characteristics of CSCs in HNSCC. We summarize current approaches used in the literature for identification of HNSCC CSCs, and mechanisms required for CSC regulation. We also highlight the role of CSCs in treatment failure and therapeutic targeting options for eliminating CSCs in HNSCC.

scholarly journals The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Amit Shah ◽  
Shilpa Patel ◽  
Jigna Pathak ◽  
Niharika Swain ◽  
Shwetha Kumar
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Neck Squamous Cell Carcinoma

There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)—the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. The present review is an attempt to conceptualize the role of CSCs in HNSCC—its implication in tumorigenesis and the possible additional approach in current treatment strategies.

scholarly journals Cancer Epigenomics and Beyond: Advancing the Precision Oncology Paradigm

2020 ◽  
Vol 3 (4) ◽  
pp. 147-156
Author(s):  
Daniel Y. Lee
Keyword(s):  
Large Scale ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Precision Oncology ◽  
Immunomodulatory Agents ◽  
Regulatory Pathways ◽  
Fundamental Process ◽  
Genomics Tools ◽  
Tools And Techniques ◽  
Cancer Epigenomics

ABSTRACT How cancers are characterized and treated has evolved over the past few decades. Major advances in genomics tools and techniques have revealed interlinked regulatory pathways of cancers with unprecedented detail. Early discoveries led to success with rationally targeted small molecules and more recently with immunomodulatory agents, setting the stage for precision oncology. However, drug resistance to every agent has thus far proven intractable, sending us back to fill the gaps in our rudimentary knowledge of tumor biology. Epigenetics is emerging as a fundamental process in every hallmark of cancer. Large-scale interrogation of the cancer epigenome continues to reveal new mechanisms of astounding complexity. In this review, I present selected experimental and clinical examples that have shaped our understanding of cancer at the molecular level. Translation of our collective erudition into revolutionary diagnostic and treatment strategies will advance the precision oncology paradigm.

Decoding Novel Mechanisms and Emerging Therapeutic Strategies in Breast Cancer Resistance

2020 ◽  
Vol 21 (3) ◽  
pp. 199-210 ◽  
Author(s):  
Sadat Shafi ◽  
Sana Khan ◽  
Farazul Hoda ◽  
Faizana Fayaz ◽  
Archu Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Gene Therapy ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Cancer Resistance ◽  
Therapeutic Approaches ◽  
Efficient Treatment ◽  
Cancer Theranostics

Breast cancer (BC), an intricate and highly heterogeneous disorder, has presently afflicted 2.09 million females globally. Chemoresistance remains a paramount challenge in the treatment of BC. Owing to its assorted nature, the chemoresistant mechanisms of BC still need intensive research. Accumulating evidence suggests that abnormalities related to the biogenesis of cancer stem cells (CSCs) and microRNAs (miRNAs) are associated with BC progression and chemoresistance. The presently available interventions are inadequate to target chemoresistance, therefore more efficient alternatives are urgently needed to improvise existing therapeutic regimens. A myriad of strategies is being explored, such as immunotherapy, gene therapy, and combination treatment to surmount chemoresistance. Additionally, nanoparticles as chemotherapeutic carriers put forward the options to encapsulate numerous drugs, alone as well as in combination for cancer theranostics. This review summarizes the chemoresistance mechanisms of miRNAs and CSCs as well as the most recently documented therapeutic approaches for the treatment of chemoresistance in BC. By unraveling the underpinning mechanism of BC chemoresistance, researchers could possibly develop more efficient treatment strategies towards BC.

scholarly journals TMOD-41. ORTHOTOPIC PATIENT-DERIVED XENOGRAFT MODELS OF BRAIN METASTASIS: PLATFORMS FOR PRECISION ONCOLOGY AND UNDERSTANDING TUMOR BIOLOGY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi272-vi272
Author(s):  
Matthew Dankner ◽  
Paul Savage ◽  
April Rose ◽  
Mathieu Lajoie ◽  
Roberto Diaz ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Class Ii ◽  
Precision Oncology ◽  
Survival Times ◽  
Mesenchymal Transition ◽  
Braf Mutant

Abstract RATIONALE Brain metastasis (BrM) occurs in 10–20% of cancer patients and results in median survival times of less than 1 year. In order to accurately develop novel treatment strategies, there is an urgent need to establish animal models of BrM that resemble the human disease. OBJECTIVES: We sought to establish orthotopic patient-derived xenografts (PDX) models of BrM from diverse solid cancers to understand biological characteristics of BrM and to test novel drug candidates in their ability to treat BrM. METHODS 35 PDXs were established by subcutaneous or mammary fat pad implantation and by intracranial injection. PDXs were validated by immunohistochemistry of routine pathological markers in patient specimens and matched primary and intracranial PDXs. PDXs were applied for precision medicine in class II BRAF mutant tumours treated with targeted therapy and in the pre-clinical development of a novel therapeutic agent, DZ-2384, which may have applications in treating BrM. They were also used to understand the underlying biology of leptomeningeal dissemination from parenchymal BrM. RESULTS PDXs reveal strong similarity to patient specimens by IHC staining. Class II BRAF mutant PDXs are optimally sensitive to BRAF and MEK inhibitors compared to either agent alone. DZ-2384 is effective in slowing the progression of breast cancer BrM. PDXs that most efficiently invade the leptomeninges display loss of E-Cadherin expression, suggesting the role of an epithelial-mesenchymal transition in this process. CONCLUSIONS PDXs of BrM represent important models that can be employed to test novel therapeutics and to improve understanding of molecular mechanisms engaged by BrM.

Molecular Mechanisms Underlying the Functions of Cellular Markers Associated with the Phenotype of Cancer Stem Cells

2019 ◽  
Vol 14 (5) ◽  
pp. 405-420 ◽  
Author(s):  
Eduardo Alvarado-Ortiz ◽  
Miguel Á. Sarabia-Sánchez ◽  
Alejandro García-Carrancá
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Tumor Biology ◽  
Molecular Tools ◽  
Recent Past ◽  
Functional Roles ◽  
Cellular Population ◽  
Cellular Markers ◽  
A Minor

Cancer Stem Cells (CSC) generally constitute a minor cellular population within tumors that exhibits some capacities of normal Stem Cells (SC). The existence of CSC, able to self-renew and differentiate, influences central aspects of tumor biology, in part because they can continue tumor growth, give rise to metastasis, and acquire drug and radioresistance, which open new avenues for therapeutics. It is well known that SC constantly interacts with their niche, which includes mesenchymal cells, extracellular ligands, and the Extra Cellular Matrix (ECM). These interactions regularly lead to homeostasis and maintenance of SC characteristics. However, the exact participation of each of these components for CSC maintenance is not clear, as they appear to be context- or cell-specific. In the recent past, surface cellular markers have been fundamental molecular tools for identifying CSC and distinguishing them from other tumor cells. Importantly, some of these cellular markers have been shown to possess functional roles that affect central aspects of CSC. Likewise, some of these markers can participate in regulating the interaction of CSC with their niche, particularly the ECM. We focused this review on the molecular mechanisms of surface cellular markers commonly employed to identify CSC, highlighting the signaling pathways and mechanisms involved in CSC-ECM interactions, through each of the cellular markers commonly used in the study of CSC, such as CD44, CD133, CD49f, CD24, CXCR4, and LGR5. Their presence does not necessarily implicate them in CSC biology.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

Sign in / Sign up

Export Citation Format

Share Document