scholarly journals Synergistic Antitumor Activity of SH003 and Docetaxel via EGFR Signaling Inhibition in Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8405
Author(s):  
Mi-So Jeong ◽  
Kang-Wook Lee ◽  
Yu-Jeong Choi ◽  
Yun-Gyeong Kim ◽  
Hyun-Ha Hwang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Apoptotic Cell ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Tumor Xenograft ◽  
Small Cell Lung ◽  
Anticancer Effects

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.

scholarly journals Mechanisms of Resistance to EGFR TKIs and Development of a New Generation of Drugs in Non-Small-Cell Lung Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Takayuki Kosaka ◽  
Ei Yamaki ◽  
Akira Mogi ◽  
Hiroyuki Kuwano
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Clinical Problem ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tkis

Gefitinib and erlotinib, which are epidermal growth factor receptor- (EGFR-) specific tyrosine kinase inhibitors (TKIs), are widely used as molecularly targeted drugs for non-small-cell lung cancer (NSCLC). Currently, the search forEGFRgene mutations is becoming essential for the treatment of NSCLC since these have been identified as predictive factors for drug sensitivity. On the other hand, in almost all patients responsive to EGFR-TKIs, acquired resistance is a major clinical problem. Mechanisms of acquired resistance reported in the past few years include secondary mutation of theEGFRgene, amplification of theMETgene, and overexpression of HGF; novel pharmaceutical agents are currently being developed to overcome resistance. This review focuses on these mechanisms of acquired resistance to EGFR-TKIs and discusses how they can be overcome.

scholarly journals ASCO 2021—selection of personal highlights in early stage non-small cell lung cancer

2021 ◽  
Author(s):  
Gudrun Absenger ◽  
Andreas Pircher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Adjuvant Setting ◽  
Small Cell Lung ◽  
Early Stage Nsclc

SummaryThis article intends to summarize personal non-small cell lung cancer (NSCLC) highlights of the virtual ASCO 2021 meeting. Immunotherapy is now a mainstay of advanced stage NSCLC treatment and there are several ongoing studies investigating the role of immunotherapy in early stage NSCLC. At ASCO 2021 the first data on atezolizumab in the adjuvant setting were presented and give a positive signal that immunotherapy will also become an option for patient in early stage NSCLC. Furthermore, overall survival (OS) updates of two studies investigating the effects of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant setting of EGFR-mutated NSCLC patients were presented. In conclusion ASCO 2021 provided the lung cancer community with inspiring new data especial in early stages and challenges the community with integration of these data into our daily clinical routine.

Role of Cytomorphology in the Era of Liquid Biopsy

2019 ◽  
Vol 63 (6) ◽  
pp. 497-505 ◽  
Author(s):  
Eduardo Clery ◽  
Pasquale Pisapia ◽  
Elena Vigliar ◽  
Umberto Malapelle ◽  
Claudio Bellevicine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Morphological Changes ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung

In the late stages of non-small cell lung cancer, the detection of sensitizing mutations of the epidermal growth factor receptor (EGFR) is mandatory to select patients’ treatment with first- or second-generation tyrosine kinase inhibitors (TKIs). In patients showing progressive disease, the assessment of the EGFR exon 20 resistance point mutation p.T790M is required for third-generation TKI administration. However, molecular analysis does not capture all the different mechanisms of resistance against these molecules. A variety of morphological changes associated with acquired resistance have also been described. Since an altered morphology may be the only clue to acquired resistance, cytopathology still plays a relevant role in this setting. In this comprehensive review, we have focused on the relevance of squamous cell carcinoma, small cell lung cancer and large-cell neuroendocrine carcinoma transitions from adenocarcinoma resistant to TKIs.

Response to Osimertinib in a Patient With Non-Small Cell Lung Cancer and Two Uncommon EGFR mutations

2020 ◽  
pp. 10-13
Author(s):  
Christoforos Astaras ◽  
Adrienne Bettini ◽  
Daniel C. Betticher
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20

In advanced non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations are one of the most frequent oncogenic drivers. They confer a favorable prognosis and strongly predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Over the last decades, several EGFR genetic alterations, common and uncommon mutations, have been described in exons 18−21. Common mutations are exon 19 deletions (most frequently E746-A750) and exon 21 L858R substitution. Uncommon mutations include exon 18 G719X, exon 20 S768l, exon 21 L861Q and many other rare ones. This report describes the case of a 55-year-old woman with a newly diagnosed metastatic lung adenocarcinoma harboring two rare EGFR mutations and showing sustained response to osimertinib.

scholarly journals Severe gastrointestinal bleeding due to erlotinib and celecoxib therapy: additional effect?

2016 ◽  
Vol 10 ◽  
Author(s):  
Maddalena Zippi ◽  
Angeloluca De Quarto ◽  
Chiara Marzano ◽  
Claudio Cassieri ◽  
Pietro Crispino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Prior History ◽  
Small Cell Lung ◽  
Increased Risk ◽  
Egfr Tkis

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related dead worldwide and account for over 85% of all lung cancers. Furthermore, the majority of patients with NSCLC present with advanced, metastatic disease at the time of diagnosis. For most patients with non-small cell lung cancer, current treatments do not cure the cancer. Therefore, there is a great need for development of more effective therapies. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) like erlotinib and gefitinib have been recognized as an important molecular target in cancer therapy and they are approved for the treatment of refractory advanced NSCLC patients. EGFR TKIs are generally well tolerated. The two most common toxicities include dermatologic and gastrointestinal side effects. Cases of gastrointestinal perforation, some of which were fatal, have also been reported in patients receiving erlotinib. Those at increased risk include those taking concomitant anti-angiogenic agents, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease.

scholarly journals Modern vector in treatment of patients with lung cancer: tyrosine kinase inhibitors in epidermal growth factor receptor mutations (literature review)

2021 ◽  
Vol 26 (2) ◽  
pp. 4-11
Author(s):  
O.M. Smorodska ◽  
Yu.V. Moskalenko ◽  
I.O. Vynnychenko ◽  
O.I. Vynnychenko ◽  
V.V. Kostuchenko
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Egfr Tki

Tumor molecular profiling in patients with non-small cell lung cancer (NSCLC) is used to identify driver mutations, which lead to premature carcinogenesis in more than 80% of adenocarcinoma cases, including epidermal growth factor receptor (EGFR) mutations. Identification of specific somatic aberrations allows to personalize treatment. Personalization of treatment resulted in improvement of NSCLC outcomes. The aim of our study was to consider scientific data on modern concepts of treatment of patients with non-small cell lung cancer with previously detected oncogenic mutations, especially EGFR mutation. In our study we analyzed scientific papers and data of international scientific literature on the problem of lung cancer treatment. Methods used: scientific research, analytical and generalizing. Different drugs are used in treatment of lung cancer. Choice of treatment scheme depends on type and presence of mutations. Patients with advanced non-small-cell lung cancer and detected mutation in the EGFR can be treated with tyrosine kinase inhibitors (TKIs). Nowadays three first generation drugs are recommended by FDA: afatinib, erlotinib, gefitinib. They showed good clinical benefit. Most patients with metastatic NSCLC typically show disease progression after approximately 9 to 13 months of erlotinib, gefitinib, or afatinib therapy. The first and only commercially available third-generation EGFR TKI is оsimertinib - an oral drug, which selectively inhibits both EGFR-TKI and EGFR T790M resistance mutations. Nowadays scientists are in active investigation of mechanisms of acquired resistance to TKIs, but little is known yet. Clinical success can be observed in patients who were treated with TKIs. EGFR T790M is a mutation that leads to acquired resistance to EGFR TKI therapy. Its incidence is approximately 60% after disease progression on TKI drugs (erlotinib, gefitinib, or aphatinib). Third-generation EGFR TKIs demonstrate high efficacy, but acquired resistance development cannot be avoided. Mechanisms of acquired resistance to these agents are still investigated.

scholarly journals Synergistic Anticancer Effects of Curcumin and Hinokitiol on Gefitinib Resistant Non-Small Cell Lung Cancer Cells

2018 ◽  
Vol 13 (12) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Tae-Bok Lee ◽  
Eun-Ju Seo ◽  
Ji-Yun Lee ◽  
Jin Hyun Jun
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anticancer Effects ◽  
Gefitinib Resistance

This study evaluated the synergistic effect of curcumin (diferuloylmethane) and hinokitiol (β-thujaplicin), natural product derived phytochemicals, on gefitinib (Iressa) resistant non-small cell lung cancer (NSCLC) cells. Gefitinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR), is widely used for lung cancer treatment. However, gefitinib resistance is easily acquired by NSCLC and followed by the development of progressive disease. Curcumin and hinokitiol are well-known bioactive compounds demonstrating anti-inflammation, anti-bacteria and anticancer effects. However, the effects of co-treatment of curcumin and hinokitiol on cancer cells have not been reported. Here, we postulated, for the first time, the possibility of combination therapy with curcumin and hinokitiol for treatment of gefitinib resistant NSCLC via increment of apoptosis and lysosomal enlargement.

Histologic transformation to small-cell lung cancer following gefitinib and radiotherapy in a patient with pulmonary adenocarcinoma

2019 ◽  
Vol 105 (6) ◽  
pp. NP12-NP16
Author(s):  
Michele Fiore ◽  
Pasquale Trecca ◽  
Giuseppe Perrone ◽  
Michelina Amato ◽  
Daniela Righi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Resistance Mechanism ◽  
Growth Factor Receptor ◽  
Initial Response ◽  
Small Cell ◽  
Small Cell Lung

Introduction: Targeted therapies against epidermal growth factor receptor (EGFR) have revolutionized the treatment of a subset of lung adenocarcinomas that have EGFR-activating mutations; however, all patients treated with EGFR tyrosine kinase inhibitors (TKIs) ultimately develop resistance. Histologic transformation of EGFR-mutant adenocarcinoma to small cell lung cancer (SCLC) is a resistance mechanism rarely reported in the literature. Case presentation: We describe the case of a woman with metastatic lung cancer adenocarcinoma with mutated EGFR with an initial response to gefitinib and radiation therapy, who progressed after 18 months due to the development of a resistance mechanism. The new biopsy performed after progression highlighted histologic transformation to SCLC, while maintaining the original EGFR mutation. Conclusions: To better identify patients who progress after TKIs and radiation therapy, it is important to perform tumor rebiopsy and collect data to study mechanisms of acquired EGFR TKI resistance.

scholarly journals Nile Tilapia Derived TP4 Shows Broad Cytotoxicity Toward to Non-Small-Cell Lung Cancer Cells

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 506 ◽  
Author(s):  
Chen-Hung Ting ◽  
Jyh-Yih Chen
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Nile Tilapia ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Genetic Profiles

Non-small cell lung cancer (NSCLC) is among the leading causes of human mortality due to a lack of effective treatments. Conventional chemotherapies affect healthy cells and cause multidrug resistance, while tumors may eventually develop resistance to less-toxic targeted therapies. Thus, the need to develop novel therapies for NSCLC is urgent. Here, we show that Nile tilapia-derived Tilapia piscidin (TP) 4 is cytotoxic to a panel of NSCLC cells with different genetic profiles. We observed that TP4 triggers NSCLC cell death through the necrosis and combining TP4 with potent Epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKI)s, Erlotinib, and Gefitinib, improved drug responses in EGFR-mutated NSCLC cells, but not in EGFR-wild-type NSCLC cells. This work provides novel insights into potential NSCLC treatments, which may utilize antimicrobial peptide TP4 as monotherapy or in combination with EGFR-TKIs.

scholarly journals Development and characterization of ethyl cellulose nanosponges for sustained release of brigatinib for the treatment of non-small cell lung cancer

2020 ◽  
Vol 40 (10) ◽  
pp. 823-832
Author(s):  
Mohammed Muqtader Ahmed ◽  
Farhat Fatima ◽  
Md. Khalid Anwer ◽  
Mohammad Javed Ansari ◽  
Sabya Sachi Das ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Drug Loading ◽  
Growth Factor Receptor ◽  
Entrapment Efficiency ◽  
Small Cell ◽  
Human Lung Cancer ◽  
Small Cell Lung

AbstractNon-small cell lung cancer (NSCLC) contributes to about 85% of lung cancer. By 2040, lung cancer cases estimated to rise to 3.6 million globally. Brigatinib (BG) acts as tyrosine kinase inhibitors that target the epidermal growth factor receptor of the epithelial lung cancer cells. BG loaded nanosponges (NSs) were prepared by the emulsion solvent evaporation technique using ethylcellulose (EC) and polyvinyl alcohol (PVA) as a stabilizer. Eight formulations were developed by varying the concentration of the drug (BG), EC and PVA followed by optimization through particle characterization; size, polydispersity index (PDI), zeta potential (ZP), drug entrapment and loading efficiency. The optimized formulation BGNS5 showed particles size (261.0 ± 3.5 nm), PDI (0.301) and ZP(−19.83 ± 0.06 Mv) together with entrapment efficiency (85.69 ± 0.04%) and drug loading (17.69 ± 0.01%). FTIR, DSC, XRD, and SEM showed drug-polymer compatibility, entrapment of drug in EC core, non-crystallinity of BG in NS and confirm spherical porous nature of the NS. BGNS5 reflects drug release in a sustained manner, 86.91 ± 2.12% for about 12 h. BGNS5 significantly decreased the cell viability of A549 human lung cancer cell lines with less hemolytic ratio compared to pure drug BG and EC. Based on the aforementioned results BGNS5 could be used in the effective treatment of NSCLC.

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