scholarly journals Biological Adaptations of Tumor Cells to Radiation Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Angeles Carlos-Reyes ◽  
Marcos A. Muñiz-Lino ◽  
Susana Romero-Garcia ◽  
César López-Camarillo ◽  
Olga N. Hernández-de la Cruz
Keyword(s):  
Dna Repair ◽  
Radiation Therapy ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cell Damage ◽  
Antitumor Therapy ◽  
Genome Damage ◽  
Different Types ◽  
Repair Mechanisms ◽  
Cell Death Mechanisms

Radiation therapy has been used worldwide for many decades as a therapeutic regimen for the treatment of different types of cancer. Just over 50% of cancer patients are treated with radiotherapy alone or with other types of antitumor therapy. Radiation can induce different types of cell damage: directly, it can induce DNA single- and double-strand breaks; indirectly, it can induce the formation of free radicals, which can interact with different components of cells, including the genome, promoting structural alterations. During treatment, radiosensitive tumor cells decrease their rate of cell proliferation through cell cycle arrest stimulated by DNA damage. Then, DNA repair mechanisms are turned on to alleviate the damage, but cell death mechanisms are activated if damage persists and cannot be repaired. Interestingly, some cells can evade apoptosis because genome damage triggers the cellular overactivation of some DNA repair pathways. Additionally, some surviving cells exposed to radiation may have alterations in the expression of tumor suppressor genes and oncogenes, enhancing different hallmarks of cancer, such as migration, invasion, and metastasis. The activation of these genetic pathways and other epigenetic and structural cellular changes in the irradiated cells and extracellular factors, such as the tumor microenvironment, is crucial in developing tumor radioresistance. The tumor microenvironment is largely responsible for the poor efficacy of antitumor therapy, tumor relapse, and poor prognosis observed in some patients. In this review, we describe strategies that tumor cells use to respond to radiation stress, adapt, and proliferate after radiotherapy, promoting the appearance of tumor radioresistance. Also, we discuss the clinical impact of radioresistance in patient outcomes. Knowledge of such cellular strategies could help the development of new clinical interventions, increasing the radiosensitization of tumor cells, improving the effectiveness of these therapies, and increasing the survival of patients.

scholarly journals DNA Damage Response in Multiple Myeloma: The Role of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Takayuki Saitoh ◽  
Tsukasa Oda
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Dna Repair ◽  
Tumor Microenvironment ◽  
Dna Damage Response ◽  
Genetic Instability ◽  
Dna Repair Mechanisms ◽  
Damage Response ◽  
Repair Mechanisms

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.

Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

2021 ◽  
Vol 22 ◽  
Author(s):  
Soheila Montazersaheb ◽  
Ezzatollah Fathi ◽  
Ayoub Mamandi ◽  
Raheleh Farahzadi ◽  
Hamid Reza Heidari
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Therapeutic Interventions ◽  
Tumorigenic Potential ◽  
Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

scholarly journals TR-04 * NANOPARTICLE siRNA DELIVERY VEHICLES INHIBIT DNA REPAIR AND SENSITIZE PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY

2015 ◽  
Vol 17 (suppl 3) ◽  
pp. iii37-iii37
Author(s):  
F. Kievit ◽  
Z. Stephen ◽  
K. Wang ◽  
C. Dayringer ◽  
J. Silber ◽  
...  
Keyword(s):  
Dna Repair ◽  
Radiation Therapy ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Sirna Delivery ◽  
Pediatric Brain Tumor ◽  
Brain Tumor Cells ◽  
Delivery Vehicles ◽  
Pediatric Brain

Cellular Composition of the Tumor Microenvironment

2013 ◽  
pp. e91-e97 ◽  
Author(s):  
Stephen M. Ansell ◽  
Robert H. Vonderheide
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Blood Vessels ◽  
Tumor Cells ◽  
Hematologic Malignancies ◽  
Secreted Proteins ◽  
Malignant Cells ◽  
Cellular Composition ◽  
Different Types ◽  
And Function

In addition to malignant cells, the tumor microenvironment also includes nonmalignant cells, secreted proteins, and blood vessels that surround and support the growth of the tumor. Interactions between the various components of the tumor microenvironment are significant; tumor cells can change the nature of the microenvironment, and conversely, the microenvironment can affect how a tumor grows and spreads. The structure and composition of the tumor microenvironment varies among different types of cancers and between patients. This paper focuses on the composition and function of the tumor microenvironment in hematologic malignancies with a specific focus on B-cell lymphomas.

scholarly journals NT-16 * NANOPARTICLE-MEDIATED DELIVERY OF ANTI-Ape1 siRNA SENSITIZES PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY BY INHIBITING DNA REPAIR

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v162-v162
Author(s):  
F. Kievit ◽  
Z. Stephen ◽  
K. Wang ◽  
C. Dayringer ◽  
R. Ellenbogen ◽  
...  
Keyword(s):  
Dna Repair ◽  
Radiation Therapy ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Pediatric Brain Tumor ◽  
Brain Tumor Cells ◽  
Pediatric Brain

Nanotherapy Targeting the Tumor Microenvironment

2019 ◽  
Vol 19 (7) ◽  
pp. 525-533 ◽  
Author(s):  
Bo-Shen Gong ◽  
Rui Wang ◽  
Hong-Xia Xu ◽  
Ming-Yong Miao ◽  
Zhen-Zhen Yao
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Necessary Conditions ◽  
Rapid Development ◽  
Therapeutic Effects ◽  
Tumor Resistance ◽  
Invasion And Metastasis ◽  
Passive Targeting ◽  
Different Types

Cancer is characterized by high mortality and low curability. Recent studies have shown that the mechanism of tumor resistance involves not only endogenous changes to tumor cells, but also to the tumor microenvironment (TME), which provides the necessary conditions for the growth, invasion, and metastasis of cancer cells, akin to Stephen Paget’s hypothesis of “seed and soil.” Hence, the TME is a significant target for cancer therapy via nanoparticles, which can carry different kinds of drugs targeting different types or stages of tumors. The key step of nanotherapy is the achievement of accurate active or passive targeting to trigger drugs precisely at tumor cells, with less toxicity and fewer side effects. With deepened understanding of the tumor microenvironment and rapid development of the nanomaterial industry, the mechanisms of nanotherapy could be individualized according to the specific TME characteristics, including low pH, cancer-associated fibroblasts (CAFs), and increased expression of metalloproteinase. However, some abnormal features of the TME limit drugs from reaching all tumor cells in lethal concentrations, and the characteristics of tumors vary in numerous ways, resulting in great challenges for the clinical application of nanotherapy. In this review, we discuss the essential role of the tumor microenvironment in the genesis and development of tumors, as well as the measures required to improve the therapeutic effects of tumor microenvironment-targeting nanoparticles and ways to reduce damage to normal tissue.

scholarly journals RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1561 ◽  
Author(s):  
Toma ◽  
Sullivan-Reed ◽  
Śliwiński ◽  
Skorski
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Synthetic Lethality ◽  
Lethal Effect ◽  
Drug Induced ◽  
Synthetic Lethal ◽  
Repair Mechanisms ◽  
Cancer Tumor

Alterations in DNA repair systems play a key role in the induction and progression of cancer. Tumor-specific defects in DNA repair mechanisms and activation of alternative repair routes create the opportunity to employ a phenomenon called “synthetic lethality” to eliminate cancer cells. Targeting the backup pathways may amplify endogenous and drug-induced DNA damage and lead to specific eradication of cancer cells. So far, the synthetic lethal interaction between BRCA1/2 and PARP1 has been successfully applied as an anticancer treatment. Although PARP1 constitutes a promising target in the treatment of tumors harboring deficiencies in BRCA1/2—mediated homologous recombination (HR), some tumor cells survive, resulting in disease relapse. It has been suggested that alternative RAD52-mediated HR can protect BRCA1/2-deficient cells from the accumulation of DNA damage and the synthetic lethal effect of PARPi. Thus, simultaneous inhibition of RAD52 and PARP1 might result in a robust dual synthetic lethality, effectively eradicating BRCA1/2-deficient tumor cells. In this review, we will discuss the role of RAD52 and its potential application in synthetic lethality-based anticancer therapies.

scholarly journals Exosomal Non-coding RNAs-Mediated Crosstalk in the Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Chen ◽  
Yuefeng Li ◽  
Yueqin Liu ◽  
Wenlin Xu ◽  
Xiaolan Zhu
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Early Stage ◽  
Circular Rnas ◽  
Biological Processes ◽  
Tumor Cell Growth ◽  
Different Types ◽  
Non Coding Rnas ◽  
Regulatory Functions

Exosomes are secreted by different types of cells in tumor microenvironment (TME) and participate in multiple biological processes of tumors. Non-coding RNAs (ncRNAs) enveloped in exosomes and released to the TME are shown to be involved in tumorigenesis and development, as well as act as important intracellular communication mediators. However, the understanding on the exact regulatory functions and substrates of exosomal RNA is still at an early stage. In this review, we provided an overview on recent studies on exosomes mediating the modulation of both tumor cells and immune cells, then summarized the exosomal ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)] secreted by tumor cells and stromal cells that exhibited potential capabilities to regulate tumor cell growth, progression, metastasis, drug resistance, and immune response. Our review may hopefully inspire a deeper understanding on the ncRNAs’ function as useful biomarkers for the diagnosis, prognosis, and as novel targets therapy for cancer.

Resistance against PSMA-targeting alpha-radiation therapy coincides with mutations in DNA-repair associated genes

2019 ◽  
Author(s):  
C Kratochwil ◽  
CP Heussel ◽  
F Bruchertseifer ◽  
U Haberkorn ◽  
A Morgenstern ◽  
...  
Keyword(s):  
Dna Repair ◽  
Radiation Therapy ◽  
Alpha Radiation
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