scholarly journals Advanced Human In vitro Models for the Discovery and Development of Lung Cancer Therapies

10.5772/60606 ◽  
2015 ◽  
Author(s):  
Samuel Constant ◽  
Song Huang ◽  
Ludovic Wisniewski ◽  
Christophe Mas
Keyword(s):  
Lung Cancer ◽  
In Vitro Models ◽  
Cancer Therapies

scholarly journals Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 141
Author(s):  
Iwona Ziółkowska-Suchanek
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Hypoxia ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Small Cell ◽  
Small Cell Lung ◽  
Multicellular Tumor Spheroid

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

scholarly journals Combating Acquired Resistance to Tyrosine Kinase Inhibitors in Lung Cancer

2015 ◽  
pp. e165-e173 ◽  
Author(s):  
Christine M. Lovly
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Initial Response ◽  
In Vitro Models ◽  
Tumor Biopsy

The prospective identification and therapeutic targeting of oncogenic tyrosine kinases with tyrosine kinase inhibitors (TKIs) has revolutionized the treatment for patients with non–small cell lung cancer (NSCLC). TKI therapy frequently induces dramatic clinical responses in molecularly defined cohorts of patients with lung cancer, paving the way for the implementation of precision medicine. Unfortunately, acquired resistance, defined as tumor progression after initial response, seems to be an inevitable consequence of this treatment approach. This brief review will provide an overview of the complex and heterogeneous problem of acquired resistance to TKI therapy in NSCLC, with a focus on EGFR-mutant and ALK-rearranged NSCLC. In vitro models of TKI resistance and analysis of tumor biopsy samples at the time of disease progression have generated breakthroughs in our understanding of the spectrum of mechanisms by which a tumor can thwart TKI therapy and have provided an important rationale for the development of novel approaches to delay or overcome resistance. Numerous ongoing clinical trials implement strategies, including novel, more potent TKIs and rational combinations of targeted therapies, some of which have already proven effective in surmounting therapeutic resistance.

Abstract 1993: Off-target effects of ultra-low dose dimethyl sulfoxide on targetable signaling events in lung cancer in vitro models

2021 ◽  
Author(s):  
Elisa Baldelli ◽  
Mahalakshmi Subramanian ◽  
Abduljalil M. Alsubaie ◽  
Sara Baglivo ◽  
K A. Hodge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dimethyl Sulfoxide ◽  
Low Dose ◽  
In Vitro Models ◽  
Signaling Events ◽  
Target Effects

scholarly journals Lung Cancer Stem Cell: New Insights on Experimental Models and Preclinical Data

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Caroline Rivera ◽  
Sofia Rivera ◽  
Yohann Loriot ◽  
Marie-Catherine Vozenin ◽  
Eric Deutsch
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumor Development ◽  
Experimental Models ◽  
Cancer Therapies ◽  
Tumor Initiating Cells ◽  
Preclinical Data

Lung cancer remains the leading cause of cancer death. Understanding lung tumors physiopathology should provide opportunity to prevent tumor development or/and improve their therapeutic management. Cancer stem cell (CSC) theory refers to a subpopulation of cancer cells, also named tumor-initiating cells, that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signaling pathways specific to lung CSCs may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developingin vitroandin vivomodels may yield reliable tools to better understand CSC abilities and to test new therapeutic targets. Preclinical data on putative CSC targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies.

scholarly journals Advanced Nanoparticle-Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3539
Author(s):  
Noratiqah Mohtar ◽  
Thaigarajan Parumasivam ◽  
Amirah Mohd Gazzali ◽  
Chu Shan Tan ◽  
Mei Lan Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
In Vitro Models ◽  
Small Cell ◽  
The Body ◽  
Small Cell Lung ◽  
In Vivo Models ◽  
Different Types

Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.

scholarly journals Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3930
Author(s):  
Sangun Park ◽  
Tae Kim ◽  
Soo Kim ◽  
Seungkwon You ◽  
Youngmee Jung
Keyword(s):  
Lung Cancer ◽  
Extracellular Matrix ◽  
Three Dimensional ◽  
A549 Cells ◽  
Circulatory System ◽  
Lung Fibroblasts ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.

scholarly journals From Biology to Therapy: Improvements of Therapeutic Options in Lung Cancer

2019 ◽  
Vol 18 (9) ◽  
pp. 1235-1240 ◽  
Author(s):  
Luigi Formisano ◽  
Valerie M. Jansen ◽  
Roberta Marciano ◽  
Roberto Bianco
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Chemotherapeutic Agents ◽  
Cancer Therapies ◽  
In Vivo Models ◽  
Egfr Tyrosine Kinase Inhibitors

Lung cancer is the leading cause of cancer-related mortality around the world, despite effective chemotherapeutic agents, the prognosis has remained poor for a long time. The discovery of molecular changes that drive lung cancer has led to a dramatic shift in the therapeutic landscape of this disease. In “in vitro” and “in vivo” models of NSCLC (Non-Small Cell Lung Cancer), angiogenesis blockade has demonstrated an excellent anti-tumor activity, thus, a number of anti-angiogenic drugs have been approved by regulatory authorities for use in clinical practice. Much more interesting is the discovery of EGFR (Epithelial Growth Factor Receptor) mutations that predict sensitivity to the anti-EGFR Tyrosine Kinase Inhibitors (TKIs), a class of drugs that has shown to significantly improve survival when compared with standard chemotherapy in the first-line treatment of metastatic NSCLC. Nevertheless, after an initial response, resistance often occurs and prognosis becomes dismal. Biomolecular studies on cell line models have led to the discovery of mutations (e.g., T790M) that confer resistance to anti-EGFR inhibitors. Fortunately, drugs that are able to circumvent this mechanism of resistance have been developed and have been recently approved for clinical use. The discovery of robust intratumor lymphocyte infiltration in NSCLC has paved the way to several strategies able to restore the immune response. Thus, agents interfering with PD-1/PD-L1 (Programmed Death) pathways make up a significant portion of the armamentarium of cancer therapies for NSCLC. In all the above-mentioned situations, the basis of the success in treating NSCLC has started from understanding of the mutational landscape of the tumor.

scholarly journals Metabolic Switching of Tumor Cells under Hypoxic Conditions in a Tumor-on-a-chip Model

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 382 ◽  
Author(s):  
Valentina Palacio-Castañeda ◽  
Lucas Kooijman ◽  
Bastien Venzac ◽  
Wouter Verdurmen ◽  
Séverine Le Gac
Keyword(s):  
Cell Culture ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Tumor Cells ◽  
In Vitro Models ◽  
Cancer Therapies ◽  
Metabolic Switch ◽  
Hypoxic Conditions ◽  
Tumor Cell Culture

Hypoxia switches the metabolism of tumor cells and induces drug resistance. Currently, no therapeutic exists that effectively and specifically targets hypoxic cells in tumors. Development of such therapeutics critically depends on the availability of in vitro models that accurately recapitulate hypoxia as found in the tumor microenvironment. Here, we report on the design and validation of an easy-to-fabricate tumor-on-a-chip microfluidic platform that robustly emulates the hypoxic tumor microenvironment. The tumor-on-a-chip model consists of a central chamber for 3D tumor cell culture and two side channels for medium perfusion. The microfluidic device is fabricated from polydimethylsiloxane (PDMS), and oxygen diffusion in the device is blocked by an embedded sheet of polymethyl methacrylate (PMMA). Hypoxia was confirmed using oxygen-sensitive probes and the effect on the 3D tumor cell culture investigated by a pH-sensitive dual-labeled fluorescent dextran and a fluorescently labeled glucose analogue. In contrast to control devices without PMMA, PMMA-containing devices gave rise to decreases in oxygen and pH levels as well as an increased consumption of glucose after two days of culture, indicating a rapid metabolic switch of the tumor cells under hypoxic conditions towards increased glycolysis. This platform will open new avenues for testing anti-cancer therapies targeting hypoxic areas.

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