scholarly journals MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer

2016 ◽  
Vol 40 (1-2) ◽  
pp. 62-76 ◽  
Author(s):  
Tao Xie ◽  
Mengxi Huang ◽  
Ye Wang ◽  
Liya Wang ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Circulating Biomarkers ◽  
Future Directions ◽  
Effective Strategies

Chemotherapy and targeted therapy are the main options for andvanced colorectal cancer (CRC). However, resistance to these therapies is a major challenge in the clinic. Understanding molecular mechanisms and developing effective strategies against the drug resistance are highly desired. Increasing evidence has revealed that microRNAs (miRNAs) are closely linked to drug resistance in CRC. The explosion of knowledge in this field has brought forward new predictive and therapeutic opportunities. In this review, we systemically summarize the roles of miRNAs as regulators, tissue or circulating biomarkers, and therapeutics in the CRC resistance to 5-fluorouracil (5-FU), oxaliplatin and anti-EGFR therapy. We also discuss the potential unsettled issues and future directions concerning these processes.

scholarly journals MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

2021 ◽  
Vol 14 (2) ◽  
pp. 136
Author(s):  
Eunsun Jung ◽  
Jinhyeon Choi ◽  
Jang-Seong Kim ◽  
Tae-Su Han
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Therapeutic Targets ◽  
Cell Cycle Checkpoints ◽  
Drug Uptake ◽  
Cancer Drug ◽  
Drug Resistant

Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment.

scholarly journals Role of Small Molecule Targeted Compounds in Cancer: Progress, Opportunities, and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Guoqiang Sun ◽  
Dawei Rong ◽  
Zhouxiao Li ◽  
Guangshun Sun ◽  
Fan Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Drug Administration ◽  
Small Molecule ◽  
Molecular Targeted Therapy ◽  
Low Cost ◽  
Future Directions ◽  
Clinical Drug

Research on molecular targeted therapy of tumors is booming, and novel targeted therapy drugs are constantly emerging. Small molecule targeted compounds, novel targeted therapy drugs, can be administered orally as tablets among other methods, and do not draw upon genes, causing no immune response. It is easily structurally modified to make it more applicable to clinical needs, and convenient to promote due to low cost. It refers to a hotspot in the research of tumor molecular targeted therapy. In the present study, we review the current Food and Drug Administration (FDA)-approved use of small molecule targeted compounds in tumors, summarize the clinical drug resistance problems and mechanisms facing the use of small molecule targeted compounds, and predict the future directions of the evolving field.

scholarly journals Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Liu ◽  
Xiang Ao ◽  
Guoqiang Ji ◽  
Yuan Zhang ◽  
Wanpeng Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Life Quality ◽  
Therapeutic Targets ◽  
Chemotherapeutic Agents ◽  
Response To Chemotherapy ◽  
Novel Biomarkers ◽  
Related Proteins

Gastric cancer (GC) is one of the most common malignant tumors of digestive systems worldwide, with high recurrence and mortality. Chemotherapy is still the standard treatment option for GC and can effectively improve the survival and life quality of GC patients. However, with the emergence of drug resistance, the clinical application of chemotherapeutic agents has been seriously restricted in GC patients. Although the mechanisms of drug resistance have been broadly investigated, they are still largely unknown. MicroRNAs (miRNAs) are a large group of small non-coding RNAs (ncRNAs) widely involved in the occurrence and progression of many cancer types, including GC. An increasing amount of evidence suggests that miRNAs may play crucial roles in the development of drug resistance by regulating some drug resistance-related proteins as well as gene expression. Some also exhibit great potential as novel biomarkers for predicting drug response to chemotherapy and therapeutic targets for GC patients. In this review, we systematically summarize recent advances in miRNAs and focus on their molecular mechanisms in the development of drug resistance in GC progression. We also highlight the potential of drug resistance-related miRNAs as biomarkers and therapeutic targets for GC patients.

scholarly journals Pancreatic Neuroendocrine Tumors: Molecular Mechanisms and Therapeutic Targets

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5117
Author(s):  
Chandra K. Maharjan ◽  
Po Hien Ear ◽  
Catherine G. Tran ◽  
James R. Howe ◽  
Chandrikha Chandrasekharan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Neuroendocrine Tumors ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Somatostatin Receptor ◽  
Therapeutic Targets ◽  
Model Systems ◽  
Pancreatic Neuroendocrine Tumors ◽  
Acquired Drug Resistance ◽  
Molecular Alterations

Pancreatic neuroendocrine tumors (pNETs) are unique, slow-growing malignancies whose molecular pathogenesis is incompletely understood. With rising incidence of pNETs over the last four decades, larger and more comprehensive ‘omic’ analyses of patient tumors have led to a clearer picture of the pNET genomic landscape and transcriptional profiles for both primary and metastatic lesions. In pNET patients with advanced disease, those insights have guided the use of targeted therapies that inhibit activated mTOR and receptor tyrosine kinase (RTK) pathways or stimulate somatostatin receptor signaling. Such treatments have significantly benefited patients, but intrinsic or acquired drug resistance in the tumors remains a major problem that leaves few to no effective treatment options for advanced cases. This demands a better understanding of essential molecular and biological events underlying pNET growth, metastasis, and drug resistance. This review examines the known molecular alterations associated with pNET pathogenesis, identifying which changes may be drivers of the disease and, as such, relevant therapeutic targets. We also highlight areas that warrant further investigation at the biological level and discuss available model systems for pNET research. The paucity of pNET models has hampered research efforts over the years, although recently developed cell line, animal, patient-derived xenograft, and patient-derived organoid models have significantly expanded the available platforms for pNET investigations. Advancements in pNET research and understanding are expected to guide improved patient treatments.

scholarly journals The AKT/GSK3-Mediated Slug Expression Contributes to Oxaliplatin Resistance in Colorectal Cancer via Upregulation of ERCC1

2020 ◽  
Vol 28 (4) ◽  
pp. 423-438 ◽  
Author(s):  
Wei Wei ◽  
Xiao-Dong Ma ◽  
Guan-Min Jiang ◽  
Bin Shi ◽  
Wen Zhong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase 3 ◽  
First Line ◽  
Slug Expression ◽  
Simultaneous Inhibition ◽  
Ercc1 Expression ◽  
Hct116 Cells

Although oxaliplatin serves as one of the first-line drugs prescribed for treating colorectal cancer (CRC), the therapeutic effect is disappointing due to drug resistance. So far, the molecular mechanisms mediating oxaliplatin resistance remain unclear. In this study, we found the chemoresistance in oxaliplatin-resistant HCT116 cells (HCT116/OXA) was mediated by the upregulation of ERCC1 expression. In addition, the acquisition of resistance induced epithelialmesenchymal transition (EMT) as well as the Slug overexpression. On the contrary, Slug silencing reversed the EMT phenotype, decreased ERCC1 expression, and ameliorated drug resistance. Further mechanistical studies revealed the enhanced Slug expression resulted from the activation of AKT/glycogen synthase kinase 3 (GSK3) signaling. Moreover, in CRC patients, coexpression of Slug and ERCC1 was observed, and increased Slug expression was significantly correlated with clinicopathological factors and prognosis. Taken together, the simultaneous inhibition of the AKT/GSK3/Slug axis may be of significance for surmounting metastasis and chemoresistance, thereby improving the therapeutic outcome of oxaliplatin.

scholarly journals The Emerging Role of MicroRNAs in Regulating the Drug Response of Cholangiocarcinoma

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1396
Author(s):  
Wen-Kuan Huang ◽  
Chun-Nan Yeh
Keyword(s):  
Drug Resistance ◽  
Targeted Therapy ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Mesenchymal Transition

Cholangiocarcinoma (CCA) is the most common biliary malignancy, and has a poor prognosis. The median overall survival with the standard-of-care chemotherapy (Gemcitabine and cisplatin) in patients with advanced-stage CCA is less than one year. The limited efficacy of chemotherapy or targeted therapy remains a major obstacle to improving survival. The mechanisms involved in drug resistance are complex. Research efforts focusing on the distinct molecular mechanisms underlying drug resistance should prompt the development of treatment strategies that overcome chemoresistance or targeted drug resistance. MicroRNAs (miRNAs) are a class of evolutionarily conserved, short noncoding RNAs regulating gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to participate in almost all CCA hallmarks, including cell proliferation, migration and invasion, apoptosis, and the epithelial-to-mesenchymal transition. Emerging evidence demonstrates that miRNAs play a role in regulating responses to chemotherapy and targeted therapy. Herein, we present an overview of the current knowledge on the miRNA-mediated regulatory mechanisms underlying drug resistance among CCA. We also discuss the application of miRNA-based therapeutics to CCA, providing the basis for innovative treatment approaches.

scholarly journals Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer

2022 ◽  
Author(s):  
Mohamed Haider ◽  
Amr El Sherbeny ◽  
Valeria Pittalà ◽  
Antonino N. Fallica ◽  
Maha Ali Alghamdi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Therapeutic Agents ◽  
Future Directions ◽  
Significant Challenge ◽  
Cancer Occurrence ◽  
Complex Process ◽  
Anticancer Treatment ◽  
Therapeutic Alternatives

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

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