Role of microRNAs in the development of hepatocellular carcinoma and acquired drug resistance

10.2741/4734 ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 545-554 ◽  
Author(s):  
Deepak Kumar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Acquired Drug Resistance

scholarly journals Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2878
Author(s):  
Claudia Maria Hattinger ◽  
Maria Pia Patrizio ◽  
Leonardo Fantoni ◽  
Chiara Casotti ◽  
Chiara Riganti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Cure Rate ◽  
Acquired Drug Resistance ◽  
Unselected Patient ◽  
Dismal Prognosis ◽  
Non Coding Rnas ◽  
High Grade Osteosarcoma

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

scholarly journals The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Carolina Soekmadji ◽  
Colleen C. Nelson
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Advanced Prostate Cancer ◽  
Control Cell ◽  
Extracellular Vesicle ◽  
Multidrug Resistance Proteins ◽  
Acquired Drug Resistance ◽  
Resistance Proteins

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

scholarly journals Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Lakshana Sreenivasan ◽  
Hui Wang ◽  
Shyong Quin Yap ◽  
Pascal Leclair ◽  
Anthony Tam ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
Acquired Drug Resistance ◽  
Stat3 Signaling ◽  
Therapeutic Benefits ◽  
Signaling Axis ◽  
Neuronal Precursors ◽  
Cranial Fossa ◽  
Group 3

AbstractMedulloblastoma (MB) is a high-grade pediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. In this study, we evaluated the role of STAT3 and IL-6 in a tumor microenvironment mediated drug resistance in human MBs. We established that the Group 3 MB cell line, Med8A, is chemosensitive (hence Med8A-S), and this is correlated with a basal low phosphorylated state of STAT3, while treatment with IL-6 induced robust increases in pY705-STAT3. Via incremental selection with vincristine, we derived the stably chemoresistant variant, Med8A-R, that exhibited multi-drug resistance, enhanced IL-6 induced pY705-STAT3 levels, and increased IL6R expression. Consequently, abrogation of STAT3 or IL6R expression in Med8A-R led to restored chemosensitivity to vincristine, highlighting a prominent role for canonical IL-6/STAT3 signaling in acquired drug resistance. Furthermore, Med8A-S subjected to conditioning exposure with IL-6, termed Med8A-IL6+ cells, exhibited enhanced vincristine resistance, increased expression of pY705-STAT3 and IL6R, and increased secretion of IL-6. When cocultured with Med8A-IL6+ cells, Med8A-S cells exhibited increased pY705-STAT3 and increased IL-6 secretion, suggesting a cytokine feedback loop responsible for amplifying STAT3 activity. Similar IL-6 induced phenomena were also observed in the Group 3 MB cell lines, D283 and D341, including increased pY705-STAT3, drug resistance, IL-6 secretion and IL6R expression. Our study unveiled autocrine IL-6 as a promoter of STAT3 signaling in development of drug resistance, and suggests therapeutic benefits for targeting the IL-6/STAT3 signaling axis in Group 3 MBs.

scholarly journals The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ling Wei ◽  
Xingwu Wang ◽  
Liyan Lv ◽  
Jibing Liu ◽  
Huaixin Xing ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Multiple Tumor ◽  
Nucleolar Rnas

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.

scholarly journals The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2241
Author(s):  
Elizabeth L. Thompson ◽  
Jiayi J. Hu ◽  
Laura J. Niedernhofer
Keyword(s):  
Drug Resistance ◽  
Malignant Melanoma ◽  
Missense Mutation ◽  
Kinase Domain ◽  
Secondary Cancer ◽  
Braf Mutations ◽  
Acquired Drug Resistance ◽  
Survival Pathways ◽  
Progression Of Disease

BRAF is the most common gene mutated in malignant melanoma, and predominately it is a missense mutation of codon 600 in the kinase domain. This oncogenic BRAF missense mutation results in constitutive activation of the mitogen-activate protein kinase (MAPK) pro-survival pathway. Several BRAF inhibitors (BRAFi) have been developed to specifically inhibit BRAFV600 mutations that improve melanoma survival, but resistance and secondary cancer often occur. Causal mechanisms of BRAFi-induced secondary cancer and resistance have been identified through upregulation of MAPK and alternate pro-survival pathways. In addition, overriding of cellular senescence is observed throughout the progression of disease from benign nevi to malignant melanoma. In this review, we discuss melanoma BRAF mutations, the genetic mechanism of BRAFi resistance, and the evidence supporting the role of senescent cells in melanoma disease progression, drug resistance and secondary cancer. We further highlight the potential benefit of targeting senescent cells with senotherapeutics as adjuvant therapy in combating melanoma.

scholarly journals Targeting autophagy in thyroid cancers

2019 ◽  
Vol 26 (4) ◽  
pp. R181-R194 ◽  
Author(s):  
Weijun Wei ◽  
Heather Hardin ◽  
Quan-Yong Luo
Keyword(s):  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Future Research ◽  
Thyroid Cancers ◽  
Acquired Drug Resistance ◽  
Research Perspectives ◽  
Molecular Therapeutics ◽  
Dedifferentiation Process

Thyroid cancer is one of the most common endocrine malignancies. Although the prognosis for the majority of thyroid cancers is relatively good, patients with metastatic, radioiodine-refractory or anaplastic thyroid cancers have an unfavorable outcome. With the gradual understanding of the oncogenic events in thyroid cancers, molecularly targeted therapy using tyrosine kinase inhibitors (TKIs) is greatly changing the therapeutic landscape of radioiodine-refractory differentiated thyroid cancers (RR-DTCs), but intrinsic and acquired drug resistance, as well as adverse effects, may limit their clinical efficacy and use. In this setting, development of synergistic treatment options is of clinical significance, which may enhance the therapeutic effect of current TKIs and further overcome the resultant drug resistance. Autophagy is a critical cellular process involved not only in protecting cells and organisms from stressors but also in the maintenance and development of various kinds of cancers. Substantial studies have explored the complex role of autophagy in thyroid cancers. Specifically, autophagy plays important roles in mediating the drug resistance of small-molecular therapeutics, in regulating the dedifferentiation process of thyroid cancers and also in affecting the treatment outcome of radioiodine therapy. Exploring how autophagy intertwines in the development and dedifferentiation process of thyroid cancers is essential, which will enable a more profound understanding of the physiopathology of thyroid cancers. More importantly, these advances may fuel future development of autophagy-targeted therapeutic strategies for patients with thyroid cancers. Herein, we summarize the most recent evidence uncovering the role of autophagy in thyroid cancers and highlight future research perspectives in this regard.

scholarly journals Insights into an Immunotherapeutic Approach to Combat Multidrug Resistance in Hepatocellular Carcinoma

2021 ◽  
Vol 14 (7) ◽  
pp. 656
Author(s):  
Aswathy R. Devan ◽  
Ayana R. Kumar ◽  
Bhagyalakshmi Nair ◽  
Nikhil Ponnoor Anto ◽  
Amitha Muraleedharan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
Resistance Mechanism ◽  
Multi Drug Resistance ◽  
Acquired Drug Resistance ◽  
High Refractoriness ◽  
Poor Patient Survival

Hepatocellular carcinoma (HCC) has emerged as one of the most lethal cancers worldwide because of its high refractoriness and multi-drug resistance to existing chemotherapies, which leads to poor patient survival. Novel pharmacological strategies to tackle HCC are based on oral multi-kinase inhibitors like sorafenib; however, the clinical use of the drug is restricted due to the limited survival rate and significant side effects, suggesting the existence of a primary or/and acquired drug-resistance mechanism. Because of this hurdle, HCC patients are forced through incomplete therapy. Although multiple approaches have been employed in parallel to overcome multidrug resistance (MDR), the results are varying with insignificant outcomes. In the past decade, cancer immunotherapy has emerged as a breakthrough approach and has played a critical role in HCC treatment. The liver is the main immune organ of the lymphatic system. Researchers utilize immunotherapy because immune evasion is considered a major reason for rapid HCC progression. Moreover, the immune response can be augmented and sustained, thus preventing cancer relapse over the post-treatment period. In this review, we provide detailed insights into the immunotherapeutic approaches to combat MDR by focusing on HCC, together with challenges in clinical translation.

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