scholarly journals Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Pamela Bielli ◽  
Vittoria Pagliarini ◽  
Marco Pieraccioli ◽  
Cinzia Caggiano ◽  
Claudio Sette
Keyword(s):  
Alternative Splicing ◽  
Brain Tumors ◽  
Current Knowledge ◽  
Tumor Biology ◽  
Cancer Therapies ◽  
Cellular Processes ◽  
Genes Encoding ◽  
Targeted Cancer Therapies ◽  
Oncogenic Driver ◽  
Intercellular Communications

Brain tumors are a heterogeneous group of neoplasms ranging from almost benign to highly aggressive phenotypes. The malignancy of these tumors mostly relies on gene expression reprogramming, which is frequently accompanied by the aberrant regulation of RNA processing mechanisms. In brain tumors, defects in alternative splicing result either from the dysregulation of expression and activity of splicing factors, or from mutations in the genes encoding splicing machinery components. Aberrant splicing regulation can generate dysfunctional proteins that lead to modification of fundamental physiological cellular processes, thus contributing to the development or progression of brain tumors. Herein, we summarize the current knowledge on splicing abnormalities in brain tumors and how these alterations contribute to the disease by sustaining proliferative signaling, escaping growth suppressors, or establishing a tumor microenvironment that fosters angiogenesis and intercellular communications. Lastly, we review recent efforts aimed at developing novel splicing-targeted cancer therapies, which employ oligonucleotide-based approaches or chemical modulators of alternative splicing that elicit an impact on brain tumor biology.

scholarly journals Breast Cancer Heterogeneity and Response to Novel Therapeutics

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3271
Author(s):  
Mariona Baliu-Piqué ◽  
Atanasio Pandiella ◽  
Alberto Ocana
Keyword(s):  
Cancer Therapy ◽  
Tumor Heterogeneity ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Phenotypic Characteristics ◽  
Cancer Heterogeneity ◽  
Targeted Cancer Therapies ◽  
Oncogenic Driver ◽  
Almost All ◽  
Tumoral Cells

Targeted cancer therapies against oncogenic drivers are actively being developed and tested in clinical trials. Targeting an oncogenic driver may only prove effective if the mutation is present in most tumoral cells. Therefore, highly heterogeneous tumors may be refractory to these therapies. This makes tumor heterogeneity a major challenge in cancer therapy. Although heterogeneity has traditionally been attributed to genetic diversity within cancer cell populations, it is now widely recognized that human cancers are heterogeneous in almost all distinguishable phenotypic characteristics. Understanding the genetic variability and also the non-genetic influences of tumor heterogeneity will provide novel insights into how to reverse therapeutic resistance and improve cancer therapy.

scholarly journals Emerging Role and Therapeutic Potential of lncRNAs in Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3843
Author(s):  
Laura Schwarzmueller ◽  
Oscar Bril ◽  
Louis Vermeulen ◽  
Nicolas Léveillé
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Cancer Therapies ◽  
Cellular Processes ◽  
Targeted Cancer Therapies ◽  
Fine Regulation ◽  
Key Events

Maintenance of the intestinal epithelium is dependent on the control of stem cell (SC) proliferation and differentiation. The fine regulation of these cellular processes requires a complex dynamic interplay between several signaling pathways, including Wnt, Notch, Hippo, EGF, Ephrin, and BMP/TGF-β. During the initiation and progression of colorectal cancer (CRC), key events, such as oncogenic mutations, influence these signaling pathways, and tilt the homeostatic balance towards proliferation and dedifferentiation. Therapeutic strategies to specifically target these deregulated signaling pathways are of particular interest. However, systemic blocking or activation of these pathways poses major risks for normal stem cell function and tissue homeostasis. Interestingly, long non-coding RNAs (lncRNAs) have recently emerged as potent regulators of key cellular processes often deregulated in cancer. Because of their exceptional tissue and tumor specificity, these regulatory RNAs represent attractive targets for cancer therapy. Here, we discuss how lncRNAs participate in the maintenance of intestinal homeostasis and how they can contribute to the deregulation of each signaling pathway in CRC. Finally, we describe currently available molecular tools to develop lncRNA-targeted cancer therapies.

scholarly journals Liquid Biomarkers for Pediatric Brain Tumors: Biological Features, Advantages and Perspectives

2020 ◽  
Vol 10 (4) ◽  
pp. 254
Author(s):  
Sibylle Madlener ◽  
Johannes Gojo
Keyword(s):  
Brain Tumors ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Clinical Care ◽  
Tumor Biology ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
Tumor Type ◽  
Molecular Alterations ◽  
Pediatric Brain

Tumors of the central nervous system are the most frequent solid tumor type and the major cause for cancer-related mortality in children and adolescents. These tumors are biologically highly heterogeneous and comprise various different entities. Molecular diagnostics are already well-established for pediatric brain tumors and have facilitated a more accurate patient stratification. The availability of targeted, biomarker-driven therapies has increased the necessity of longitudinal monitoring of molecular alterations within tumors for precision medicine-guided therapy. Nevertheless, diagnosis is still primarily based on analyses of the primary tumor and follow-up is usually performed by imaging techniques which lack important information on tumor biology possibly changing the course of the disease. To overcome this shortage of longitudinal information, liquid biopsy has emerged as a promising diagnostic tool representing a less-invasive source of biomarkers for tumor monitoring and therapeutic decision making. Novel ultrasensitive methods for detection of allele variants, genetic alterations with low abundance, have been developed and are promising tools for establishing and integrating liquid biopsy techniques into clinical routine. Pediatric brain tumors harbor multiple molecular alterations with the potential to be used as liquid biomarkers. Consequently, studies have already investigated different types of biomarker in diverse entities of pediatric brain tumors. However, there are still certain pitfalls until liquid biomarkers can be unleashed and implemented into routine clinical care. Within this review, we summarize current knowledge on liquid biopsy markers and technologies in pediatric brain tumors, their advantages and drawbacks, as well as future potential biomarkers and perspectives with respect to clinical implementation in patient care.

scholarly journals From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy

2021 ◽  
Vol 22 (11) ◽  
pp. 5574
Author(s):  
Emanuela Di Di Gregorio ◽  
Gianmaria Miolo ◽  
Asia Saorin ◽  
Agostino Steffan ◽  
Giuseppe Corona
Keyword(s):  
Cancer Metabolism ◽  
Cellular Transformation ◽  
Cancer Development ◽  
Cancer Therapies ◽  
Metabolic Intermediates ◽  
Targeted Cancer Therapies ◽  
Oncogenic Driver ◽  
Altered Metabolism ◽  
New Vision

Over the last decades, the study of cancer metabolism has returned to the forefront of cancer research and challenged the role of genetics in the understanding of cancer development. One of the major impulses of this new trend came from the discovery of oncometabolites, metabolic intermediates whose abnormal cellular accumulation triggers oncogenic signalling and tumorigenesis. These findings have led to reconsideration and support for the long-forgotten hypothesis of Warburg of altered metabolism as oncogenic driver of cancer and started a novel paradigm whereby mitochondrial metabolites play a pivotal role in malignant transformation. In this review, we describe the evolution of the cancer metabolism research from a historical perspective up to the oncometabolites discovery that spawned the new vision of cancer as a metabolic disease. The oncometabolites’ mechanisms of cellular transformation and their contribution to the development of new targeted cancer therapies together with their drawbacks are further reviewed and discussed.

scholarly journals Senolytics for Cancer Therapy: Is All that Glitters Really Gold?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 723
Author(s):  
Valerie J. Carpenter ◽  
Tareq Saleh ◽  
David A. Gewirtz
Keyword(s):  
Cancer Therapy ◽  
Tumor Cell ◽  
Cancer Therapies ◽  
Cell Models ◽  
Future Directions ◽  
Targeted Cancer Therapies

Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response to senescence-inducing conventional and targeted cancer therapies. Despite the unequivocal promise of senolytics, issues of universality, selectivity, resistance, and toxicity remain to be further clarified. In this review, we attempt to summarize and analyze the current preclinical literature involving the use of senolytics in senescent tumor cell models, and to propose tenable solutions and future directions to improve the understanding and use of this novel class of drugs.

scholarly journals Targeting Non-Oncogene Addiction for Cancer Therapy

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 129
Author(s):  
Hae Ryung Chang ◽  
Eunyoung Jung ◽  
Soobin Cho ◽  
Young-Jun Jeon ◽  
Yonghwan Kim
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Cancer Therapy ◽  
Cell Cycle Regulation ◽  
Synthetic Lethality ◽  
Current Knowledge ◽  
Cancer Therapies ◽  
Oncogene Addiction ◽  
Clinical Biomarkers ◽  
Cycle Regulation

While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of TONSL as a novel gene for targeted therapy. Although it is a scaffold protein with no known enzymatic activity, the strategy used for developing PCNA inhibitors can also be utilized to target TONSL. This review summarizes current knowledge on non-oncogene addiction, and the utilization of synthetic lethality for developing novel inhibitors targeting non-oncogenic addiction for cancer therapy.

scholarly journals An Overview of Cancer Health Disparities: New Approaches and Insights and Why They Matter

2020 ◽  
Author(s):  
Tsion Zewdu Minas ◽  
Maeve Kiely ◽  
Anuoluwapo Ajao ◽  
Stefan Ambs
Keyword(s):  
Health Care ◽  
Health Disparities ◽  
Social Stress ◽  
Access To Health Care ◽  
Health Care Disparities ◽  
Underserved Populations ◽  
Tumor Biology ◽  
Cultural Barriers ◽  
Cancer Therapies ◽  
Cancer Health Disparities

Abstract Cancer health disparities remain stubbornly entrenched in the US health care system. The Affordable Care Act was legislation to target these disparities in health outcomes. Expanded access to health care, reduction in tobacco use, uptake of other preventive measures and cancer screening, and improved cancer therapies greatly reduced cancer mortality among women and men and underserved communities in this country. Yet, disparities in cancer outcomes remain. Underserved populations continue to experience an excessive cancer burden. This burden is largely explained by health care disparities, lifestyle factors, cultural barriers, and disparate exposures to carcinogens and pathogens, as exemplified by the COVID-19 epidemic. However, research also shows that comorbidities, social stress, ancestral and immunobiological factors, and the microbiome, may contribute to health disparities in cancer risk and survival. Recent studies revealed that comorbid conditions can induce an adverse tumor biology, leading to a more aggressive disease and decreased patient survival. In this review, we will discuss unanswered questions and new opportunities in cancer health disparity research related to comorbid chronic diseases, stress signaling, the immune response, and the microbiome, and what contribution these factors may have as causes of cancer health disparities.

scholarly journals Targeting Post-Translational Modifications of the p73 Protein: A Promising Therapeutic Strategy for Tumors

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1916
Author(s):  
Ziad Omran ◽  
Mahmood H. Dalhat ◽  
Omeima Abdullah ◽  
Mohammed Kaleem ◽  
Salman Hosawi ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Protein A ◽  
P53 Gene ◽  
Cancer Therapies ◽  
Transactivation Domain ◽  
P53 Family ◽  
Post Translational Modifications ◽  
P53 Status ◽  
Apoptotic Effects ◽  
High Degree

The tumor suppressor p73 is a member of the p53 family and is expressed as different isoforms with opposing properties. The TAp73 isoforms act as tumor suppressors and have pro-apoptotic effects, whereas the ΔNp73 isoforms lack the N-terminus transactivation domain and behave as oncogenes. The TAp73 protein has a high degree of similarity with both p53 function and structure, and it induces the regulation of various genes involved in the cell cycle and apoptosis. Unlike those of the p53 gene, the mutations in the p73 gene are very rare in tumors. Cancer cells have developed several mechanisms to inhibit the activity and/or expression of p73, from the hypermethylation of its promoter to the modulation of the ratio between its pro- and anti-apoptotic isoforms. The p73 protein is also decorated by a panel of post-translational modifications, including phosphorylation, acetylation, ubiquitin proteasomal pathway modifications, and small ubiquitin-related modifier (SUMO)ylation, that regulate its transcriptional activity, subcellular localization, and stability. These modifications orchestrate the multiple anti-proliferative and pro-apoptotic functions of TAp73, thereby offering multiple promising candidates for targeted anti-cancer therapies. In this review, we summarize the current knowledge of the different pathways implicated in the regulation of TAp73 at the post-translational level. This review also highlights the growing importance of targeting the post-translational modifications of TAp73 as a promising antitumor strategy, regardless of p53 status.

scholarly journals The reimbursement of targeted cancer therapies in Bulgaria: is it evidence-based?

2015 ◽  
Vol 25 (suppl_3) ◽  
Author(s):  
T Vekov ◽  
R Koleva-Kolarova ◽  
S Aleksandrova-Yankulovska ◽  
N Veleva
Keyword(s):  
Evidence Based ◽  
Cancer Therapies ◽  
Targeted Cancer Therapies
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