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.

scholarly journals The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Norahayu Othman ◽  
Noor Hasima Nagoor
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
High Frequency ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Lung Carcinogenesis ◽  
The Past ◽  
Late Stage Diagnosis ◽  
Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

scholarly journals Drug Resistance in Non-Hodgkin Lymphomas

2020 ◽  
Vol 21 (6) ◽  
pp. 2081 ◽  
Author(s):  
Pavel Klener ◽  
Magdalena Klanova
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Front Line ◽  
Mechanisms Of Resistance ◽  
Treatment Algorithms ◽  
Acquired Drug Resistance ◽  
Complex Process ◽  
Medical Need ◽  
Druggable Targets

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

scholarly journals Exploring the effects of CDK7 inhibition by YKL-5-124 on the molecular mechanisms and the ways it triggers cytokines production in Small Cell Lung Cancer in vitro

2021 ◽  
Vol 245 ◽  
pp. 03027
Author(s):  
Weining Chen
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Target Drug ◽  
Anticancer Treatment

The previous study has researched that combining YKL-5-124, CDK7 specific target drug with anti-PD-1 treatment had a survival advantage in various Small Cell Lung Cancer models. However, the molecular mechanism that YKL-5-124 triggers inflammatory response remains unknown. This study investigates the effects of CDK7 inhibition by YKL-5-124 on two DNA damage pathways (ATM and ATR) of SCLC in vitro. The result of this study will reveal the effects of CDK7 inhibition by YKL-5-124 on the molecular mechanisms of SCLC and potentially promote the development of new anticancer treatment strategies based on immunity manipulation.

scholarly journals Actinomycin D and Telmisartan Combination Targets Lung Cancer Stem Cells Through the Wnt/Beta Catenin Pathway

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryan Green ◽  
Mark Howell ◽  
Roukiah Khalil ◽  
Rajesh Nair ◽  
Jiyu Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Actinomycin D ◽  
Inner Core ◽  
Ex Vivo ◽  
Beta Catenin ◽  
Novel Treatments

AbstractThe failure of lung cancer treatments has been attributed mostly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. Cancer initiating stem cells (CSCs), present in tumors in a small percentage, play critical roles in the development of drug resistance, metastasis, and cancer relapse. Hence, novel treatments targeting both bulk cancer cells and CSCs are under intense investigation. Herein, we report that lung cancer cells grown on a 3D fibrous scaffold form tumoroids that resemble in vivo tumors, expand CSCs, and provide a platform to identify anti-CSC drugs. The screening of an NCI library of FDA-approved drugs using tumoroid cultures led to identification of Actinomycin D (AD) as a top CSC inhibitor. Since CSCs are mostly resident in the tumor’s inner core, AD was combined with an angiotensin receptor antagonist, Telmisartan (TS), which is known to increase drug permeability in tumors and was shown to have anti-CSC activity. Our results showed that AD + TS administered intra-tumorally was significantly more effective than either drug alone in both syngeneic and xenograft mouse models. The results of mechanistic studies revealed that CSC expansion in tumoroids was associated with activation of β catenin signaling and that AD + TS treatment reduced active β catenin levels in tumors. Together, these results establish the utility of the tumoroid culture system to expand CSCs ex vivo for targeted drug screening, to identify promising novel treatments with both anti-CSC and anti-cancer effects, and to individualize treatments for metastatic drug resistant lung cancer patients.

Abstract 873: Molecular mechanisms of non-small cell lung cancer growth and drug resistance

2019 ◽  
Author(s):  
SK Kayum Alam ◽  
Matteo Astone ◽  
Ping Liu ◽  
Li Wang ◽  
Abbygail M. Coyle ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Cancer Growth ◽  
Small Cell Lung

Abstract 873: Molecular mechanisms of non-small cell lung cancer growth and drug resistance

2019 ◽  
Author(s):  
SK Kayum Alam ◽  
Matteo Astone ◽  
Ping Liu ◽  
Li Wang ◽  
Abbygail M. Coyle ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Cancer Growth ◽  
Small Cell Lung

scholarly journals Molecular Mechanisms of Pulmonary Fibrogenesis and Its Progression to Lung Cancer: A Review

2019 ◽  
Vol 20 (6) ◽  
pp. 1461 ◽  
Author(s):  
Tomonari Kinoshita ◽  
Taichiro Goto
Keyword(s):  
Lung Cancer ◽  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Therapeutic Agents ◽  
Review Article ◽  
Specific Form ◽  
Optimal Management ◽  
Current State ◽  
Novel Therapeutic

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, and limited to the lungs. Despite the increasing research interest in the pathogenesis of IPF, unfavorable survival rates remain associated with this condition. Recently, novel therapeutic agents have been shown to control the progression of IPF. However, these drugs do not improve lung function and have not been tested prospectively in patients with IPF and coexisting lung cancer, which is a common comorbidity of IPF. Optimal management of patients with IPF and lung cancer requires understanding of pathogenic mechanisms and molecular pathways that are common to both diseases. This review article reflects the current state of knowledge regarding the pathogenesis of pulmonary fibrosis and summarizes the pathways that are common to IPF and lung cancer by focusing on the molecular mechanisms.

scholarly journals Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Siyuan Luan ◽  
Xiaoxi Zeng ◽  
Chao Zhang ◽  
Jiajun Qiu ◽  
Yushang Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Esophageal Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Benefit ◽  
Therapeutic Agents ◽  
Development Of Resistance ◽  
Cellular Components

Drug resistance represents the major obstacle to get the maximum therapeutic benefit for patients with esophageal cancer since numerous patients are inherently or adaptively resistant to therapeutic agents. Notably, increasing evidence has demonstrated that drug resistance is closely related to the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic and ever-changing complex biological network whose diverse cellular and non-cellular components influence hallmarks and fates of tumor cells from the outside, and this is responsible for the development of resistance to conventional therapeutic agents to some extent. Indeed, the formation of drug resistance in esophageal cancer should be considered as a multifactorial process involving not only cancer cells themselves but cancer stem cells, tumor-associated stromal cells, hypoxia, soluble factors, extracellular vesicles, etc. Accordingly, combination therapy targeting tumor cells and tumor-favorable microenvironment represents a promising strategy to address drug resistance and get better therapeutic responses for patients with esophageal cancer. In this review, we mainly focus our discussion on molecular mechanisms that underlie the role of TME in drug resistance in esophageal cancer. We also discuss the opportunities and challenges for therapeutically targeting tumor-favorable microenvironment, such as membrane proteins, pivotal signaling pathways, and cytokines, to attenuate drug resistance in esophageal cancer.

scholarly journals Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis.

2020 ◽  
Author(s):  
Neal Shah ◽  
Zhongwei Liu ◽  
Rachel M. Tallman ◽  
Afroz Mohammad ◽  
Samuel A Sprowls ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Cardiac Ventricle

Abstract Background Cancer metastasis and drug resistance have traditionally been studied separately, though these two lethal pathological phenomena almost always occur concurrently. Brain metastasis occurs in a large proportion of lung cancer patients (~30%). Once diagnosed, patients have a poor prognosis surviving typically less than 1 year due to lack of treatment efficacy. Methods Human metastatic lung cancer cells (PC-9-Br) were injected into the left cardiac ventricle of female athymic nude mice. Brain lesions were allowed to grow for 21 days, animals were then randomized into treatment groups and treated until presentation of neurological symptoms or when moribund. Prior to tissue collection mice were injected with Oregon Green and 14C-Aminoisobutyric acid followed by an indocyanine green vascular washout. Tracer accumulation was determined by quantitative fluorescent microscopy and quantitative autoradiography. Survival was tracked and tumor burden was monitored via bioluminescent imaging. Extent of mutation differences and acquired resistance was measured in-vitro through half-maximal inhibitory assays and qRT-PCR analysis. Results A PC-9 brain seeking line (PC-9-Br) was established. Mice inoculated with PC-9-Br resulted in a significantly decreased survival time compared with mice inoculated with parental PC-9. Non-targeted chemotherapy with cisplatin and etoposide (51.5 days) significantly prolonged survival of PC-9-Br brain metastases in mice compared to vehicle control (42 days) or cisplatin and pemetrexed (45 days). Further in-vivo imaging showed greater tumor vasculature in mice treated with cisplatin and etoposide compared to non-tumor regions, which was not observed in mice treated with vehicle or cisplatin and pemetrexed. More importantly, PC-9-Br showed significant resistance to gefitinib by in-vitro MTT assays (IC50>2.5 µM at 48hrs and 0.1 µM at 72hrs) compared with parental PC-9 (IC50: 0.75 µM at 48hrs and 0.027 µM at 72hrs). Further studies on the molecular mechanisms of gefitinib resistance revealed that EGFR and phospho-EGFR were significantly decreased in PC-9-Br compared with PC-9. Expression of E-cadherin and vimentin did not show EMT in PC-9-Br compared with parental PC-9, and PC-9-Br had neither T790 mutation nor amplifications of MET and HER2 compared with parental PC-9. Conclusion Our study demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment.

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