miR-149 as a Potential Molecular Target for Cancer

2018 ◽  
Vol 25 (9) ◽  
pp. 1046-1054 ◽  
Author(s):  
Suet H. Ow ◽  
Pei J. Chua ◽  
Boon H. Bay
Keyword(s):  
Cancer Progression ◽  
Cancer Therapeutics ◽  
Molecular Target ◽  
Circular Rnas ◽  
Extensive Literature ◽  
Cancer Type ◽  
Efficient Delivery ◽  
Pubmed Database ◽  
Anti Cancer ◽  
Cancer Spread

Background: MicroRNAs (miRNAs) are frequently dysregulated in cancers and serve as attractive targets for prognostication and therapeutic applications. Besides cancer, the biological functions of miR-149 have been studied in various diseases. This review aims to summarize the reports available in the literature, regarding miR-149 as a molecular target for cancer therapeutics. Methods: An extensive literature search was conducted using the Pubmed database to sieve out articles related to the roles of miR-149 in carcinogenesis and cancer progression, and potential miRNA-based therapies. A total of 89 publications were selected for inclusion in this review. Results: Depending on the cancer type, miR-149 can behave either as a tumor suppressor or as an ‘onco-miR' that promotes tumorigenesis and cancer spread, suggesting that this miRNA has diverse functions. Potential miRNA-based therapies include the use of miRNA mimics, miRNA inhibitors, demethylating agents and circular RNAs. Conclusion: Although targeting miRNA is an attractive anti-cancer strategy, not all cancers can be treated by the same miRNA-based strategy. A comprehensive understanding of miRNA regulatory mechanism is also necessary to improve the design of miRNA-based therapeutics and there is a need for safe and efficient delivery methods when using this approach for anti-cancer treatment.

scholarly journals Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

2020 ◽  
Vol 21 (21) ◽  
pp. 7941 ◽  
Author(s):  
Lanfeng Dong ◽  
Vinod Gopalan ◽  
Olivia Holland ◽  
Jiri Neuzil
Keyword(s):  
Cancer Progression ◽  
Tricarboxylic Acid Cycle ◽  
Cancer Therapeutics ◽  
Mitochondrial Metabolism ◽  
Signalling Pathways ◽  
Transport Chain ◽  
Ros Homeostasis ◽  
Mitochondrial Functions ◽  
Anti Cancer ◽  
Selective Targeting

Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.

scholarly journals Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin/Islr in Cancer Fibrosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Masahide Takahashi ◽  
Hiroki Kobayashi ◽  
Yasuyuki Mizutani ◽  
Akitoshi Hara ◽  
Tadashi Iida ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Treatment Resistance ◽  
Cancer Therapeutics ◽  
Tumour Microenvironment ◽  
Stem Cell Marker ◽  
Desmoplastic Reaction ◽  
Colon Cancers ◽  
Anti Cancer ◽  
Bmp Signalling ◽  
Mesenchymal Stromal Stem Cell

Fibroblasts synthesise the extracellular matrix (ECM) such as collagen and elastin, the excessive accumulation of which can lead to fibrosis and organ dysfunction under pathological conditions. Cancer-associated fibroblasts (CAFs) are major constituents of the tumour microenvironment (TME) that accompany the desmoplastic reaction responsible for anti-cancer treatment resistance. Thus, it is important to dissect the roles of CAFs in the TME to develop new therapeutic strategies for refractory cancers. Recent progress in the studies of CAF biology suggests that the functions of CAFs are complicated and that they are composed of functionally distinct populations, including cancer-promoting CAFs (pCAFs) and cancer-restraining CAFs (rCAFs). We recently identified a new cell surface marker for rCAFs in pancreatic and colon cancers, designated as Meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue)/Islr (immunoglobulin super family containing leucine-rich repeat). Based on the distribution of Meflin/Islr-positive cells, we also considered it a specific candidate marker for mesenchymal stroma/stem cells. Meflin/Islr-positive CAFs have been shown to suppress cancer progression by being involved in regulating collagen structures and BMP signalling in the TME. This review describes the function of Meflin/Islr in cancer fibrosis as well as in cardiac and lung fibrosis and its potential in the development of new cancer therapeutics.

Racial composition in trials supporting the U.S. approval of anti-cancer new molecular entities (NMEs): 2011- 2016.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6518-6518 ◽  
Author(s):  
Lola A. Fashoyin-Aje ◽  
Laura L. Fernandes ◽  
Steven Lemery ◽  
Patricia Keegan ◽  
Rajeshwari Sridhara ◽  
...  
Keyword(s):  
Alaska Native ◽  
Cancer Therapeutics ◽  
Racial Composition ◽  
Cancer Type ◽  
Racial Groups ◽  
Safety And Efficacy ◽  
Black African ◽  
Asian Patients ◽  
Anti Cancer ◽  
The Us

6518 Background: In New Drug- and Biologics License Applications, clinical trials provide the primary safety and efficacy data upon which approval decisions are made. Low numbers of patients from racial groups that experience higher incidence and/or mortality from some cancers compared to the overall US population, may limit the generalizability of trial results. The Census estimates that the US population is 77.1%White, 13.3% Black/ African American (AA), 5.6% Asian, 1.2% American Indian/ Alaska Native (AIAN), and 0.2% Native Hawaiian/ Other Pacific Islander (NHPI). FDA conducted an analysis to compare the racial composition in trials supporting the approval of NMEs for the treatment of solid tumor malignancies. Methods: We reviewed the marketing applications of the 33 NMEs approved between 2011- 2016 to identify trials that provided the primary evidence of safety and efficacy. Results: A total of 29941 patients were enrolled. The table below illustrates enrollment by race (excluding Non-Hispanic, Hispanic, Other, Mixed Race & Missing) and approval year. Conclusions: The proportion of White patients enrolled in the US (88%) is higher than the proportion of Whites in the US population. However, the enrollment of AA and NHPI/AIAN patients is low and below the proportional representation of AA and NHPI/AIAN in the US. While enrollment targets may differ across cancer type and by race, the racial composition of patients enrolled in the trials that support the approval of cancer therapeutics should be reflective of the likely US patient population for whom these agents will be prescribed. The majority of Asian patients enrolled were from RoW while the majority of AA and NHPI/AIAN patients were enrolled from the US. Increasing the representation of racial minority patients in oncology trials will require targeted recruitment and enrollment of these patients in US sites. [Table: see text]

CDK1 in Breast Cancer: Implications for Theranostic Potential

2020 ◽  
Vol 20 (7) ◽  
pp. 758-767 ◽  
Author(s):  
Sepideh Izadi ◽  
Afshin Nikkhoo ◽  
Mohammad Hojjat-Farsangi ◽  
Afshin Namdar ◽  
Gholamreza Azizi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Cancer Therapeutics ◽  
Detection Methods ◽  
Breast Cancer Therapy ◽  
Promising Target ◽  
Anti Cancer

Breast cancer has been identified as one of the main cancer-related deaths among women during some last decades. Recent advances in the introduction of novel potent anti-cancer therapeutics in association with early detection methods led to a decrease in the mortality rate of breast cancer. However, the scenario of breast cancer is yet going on and further improvements in the current anti-cancer therapeutic approaches are needed. Several factors are present in the tumor microenvironment which help to cancer progression and suppression of anti-tumor responses. Targeting these cancer-promoting factors in the tumor microenvironment has been suggested as a potent immunotherapeutic approach for cancer therapy. Among the various tumorsupporting factors, Cyclin-Dependent Kinases (CDKs) are proposed as a novel promising target for cancer therapy. These factors in association with cyclins play a key role in cell cycle progression. Dysregulation of CDKs which leads to increased cell proliferation has been identified in various cancers, such as breast cancer. Accordingly, the development and use of CDK-inhibitors have been associated with encouraging results in the treatment of breast cancer. However, it is unknown that the inhibition of which CDK is the most effective strategy for breast cancer therapy. Since the selective blockage of CDK1 alone or in combination with other therapeutics has been associated with potent anti-cancer outcomes, it is suggested that CDK1 may be considered as the best CDK target for breast cancer therapy. In this review, we will discuss the role of CDK1 in breast cancer progression and treatment.

scholarly journals The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2415
Author(s):  
Yuxi Ma ◽  
Na Shen ◽  
Max S. Wicha ◽  
Ming Luo
Keyword(s):  
Cancer Progression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Treatment Resistance ◽  
Cancer Therapeutics ◽  
Circular Rnas ◽  
Cancer Therapies ◽  
Tumor Initiating Cells ◽  
Cancer Stemness ◽  
Metastatic Relapse

Cancer has long been viewed as a disease of normal development gone awry. Cancer stem-like cells (CSCs), also termed as tumor-initiating cells (TICs), are increasingly recognized as a critical tumor cell population that drives not only tumorigenesis but also cancer progression, treatment resistance and metastatic relapse. The let-7 family of microRNAs (miRNAs), first identified in C. elegans but functionally conserved from worms to human, constitutes an important class of regulators for diverse cellular functions ranging from cell proliferation, differentiation and pluripotency to cancer development and progression. Here, we review the current state of knowledge regarding the roles of let-7 miRNAs in regulating cancer stemness. We outline several key RNA-binding proteins, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) involved in the regulation of let-7 biogenesis, maturation and function. We then highlight key gene targets and signaling pathways that are regulated or mutually regulated by the let-7 family of miRNAs to modulate CSC characteristics in various types of cancer. We also summarize the existing evidence indicating distinct metabolic pathways regulated by the let-7 miRNAs to impact CSC self-renewal, differentiation and treatment resistance. Lastly, we review current preclinical studies and discuss the clinical implications for developing let-7-based replacement strategies as potential cancer therapeutics that can be delivered through different platforms to target CSCs and reduce/overcome treatment resistance when applied alone or in combination with current chemo/radiation or molecularly targeted therapies. By specifically targeting CSCs, these strategies have the potential to significantly improve the efficacy of cancer therapies.

scholarly journals Discovery and mechanistic characterization of a novel AhR receptor ligand that induces apoptosis in cancer cells

2020 ◽  
Author(s):  
Edmond O'Donnell ◽  
Hyo Sang Jang ◽  
Daniel Liefwalker ◽  
Nancy Kerkvliet ◽  
Siva Kumar Kolluri
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Fas Ligand ◽  
Cancer Therapeutics ◽  
Molecular Target ◽  
Therapeutic Interventions ◽  
Dependent Manner ◽  
New Class ◽  
Anti Cancer

Abstract Background: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and a member of the bHLH/PAS (basic Helix-Loop-Helix/Per-Arnt-Sim) family of proteins. The AhR was cloned and characterized for its role in mediating the toxicity of dioxins. Subsequent research has identified AhR’s role in the suppression of cancer cell growth. We hypothesized that that the AhR is a molecular target for therapeutic interventions, and that activation of the AhR by select AhR modulators in cancer cells could have anti-cancer properties including cell death. This study describes the discovery and characterization of a new class of anti-cancer agents targeting the AhR.Methods: We employed two independent small molecule screening approaches to identify novel modulators of the AhR with unique anti-cancer properties. We established the AhR selective effects of a highly selective modulator in cancer cells with or without the AhR expression and identified the mechanism of action of this anti-cancer compound.Results: We report the identification of CGS-15943, uniquely selective AhR modulator, that activates AhR signaling and induces apoptosis in an AhR-dependent manner in liver and breast cancer cell models. Investigation of the downstream signaling pathway of this newly identified modulator revealed novel upregulation of Fas-ligand, which is required for AhR-mediated apoptosis.Conclusions: We identified CGS-15943 as a novel AhR-selective modulator with anti-cancer properties using two parallel and distinct screening strategies. This compound induced AhR-dependent apoptosis in multiple mouse and human liver cancer cells. Our results provide a basis for the development of a new class of anti-cancer therapeutics targeting an underappreciated molecular target, the AhR.

scholarly journals Wnt/?-catenin-pathway as a molecular target for future anti-cancer therapeutics

2004 ◽  
Vol 113 (4) ◽  
pp. 515-524 ◽  
Author(s):  
Susanne Dihlmann ◽  
Magnus von Knebel Doeberitz
Keyword(s):  
Cancer Therapeutics ◽  
Molecular Target ◽  
Anti Cancer

Animal Venoms have Potential to Treat Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2555-2566 ◽  
Author(s):  
Bhaswati Chatterjee
Keyword(s):  
Cancer Therapeutics ◽  
Sea Anemones ◽  
Anticancer Activities ◽  
Inhibition Of Proliferation ◽  
Cycle Arrest ◽  
Venomous Animals ◽  
Anti Cancer ◽  
Cancerous Cells ◽  
Animal Venoms ◽  
Proteins And Peptides

The resistance to chemotherapeutics by the cancerous cells has made its treatment more complicated. Animal venoms have emerged as an alternative strategy for anti-cancer therapeutics. Animal venoms are cocktails of complex bioactive chemicals mainly disulfide-rich proteins and peptides with diverse pharmacological actions. The components of venoms are specific, stable, and potent and have the ability to modify their molecular targets thus making them good therapeutics candidates. The isolation of cancer-specific components from animal venoms is one of the exciting strategies in anti-cancer research. This review highlights the identified venom peptides and proteins from different venomous animals like snakes, scorpions, spiders, bees, wasps, snails, toads, frogs and sea anemones and their anticancer activities including inhibition of proliferation of cancer cells, their invasion, cell cycle arrest, induction of apoptosis and the identification of involved signaling pathways.

The Applications of Targeting Anti-Cancer Agents in Cancer Therapeutics

2015 ◽  
Vol 15 (7) ◽  
pp. 869-880 ◽  
Author(s):  
Guang-Chun Sun ◽  
X Yang ◽  
Yan Yu ◽  
Dai-Wei Zhao
Keyword(s):  
Cancer Therapeutics ◽  
Anti Cancer

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

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