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Targeted therapies lung cancer

Poonam Parashar, Chandra Bhushan Tripathi, Malti Arya, Jovita Kanoujia, Mahendra Singh, Abhishek Yadav, Amit Kumar, Anupam Guleria, Shubhini A Saraf
Co-therapy through biotin modified nanoparticles (NPs) of gefitinib (Gnb) and naringenin (Nar) was investigated for its therapeutic and synergistic potential against lung cancer. The biotin-conjugated polymeric NPs (bty-Nar/Gnb) were developed using oil in water emulsion technique and optimized using central composite design. The formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer. Co-administration of Gnb and Nar NPs displayed a significant reduction in tumour volume while restoring the biochemical parameters and serum metabolites to normal levels...
October 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Eunah Chung, Jae Myoung Noh, Kyu Chan Lee, Jin Hee Kim, Wonkyu Chung, Yang-Gun Suh, Jung Ae Lee, Ki Ho Seol, Hong Gyun Wu, Yeon Sil Kim, O Kyu Noh, Jae Won Park, Dong Soo Lee, Jihae Lee, Young Suk Kim, Woo-Yoon Park, Min Kyu Kang, Sunmi Jo, Yong Chan Ahn
Purpose: Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run study of the KROG 17-06 protocol...
October 15, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Huaping Tang, Lei Zhao, Meng Li, Tingtian Li, Yueqin Hao
Cyclic long noncoding RNAs have recently become major players in cancer biology and can serve as biomarkers for cancer diagnosis and prognosis, and as potential therapeutic targets. We explored circulating LINC00342 as a predictor of non-small cell lung cancer (NSCLC). The expression of LINC00342 in tissues, serum, PBMC, and NSCLC cell lines were screened by reverse transcription quantitative polymerase chain reaction. A multistage validation and risk score formula detection analysis was used. The effect of LINC00342 on proliferation was assessed by MTT, p53, and PTEN pathways, which were analyzed by Western blot analysis...
October 15, 2018: Journal of Cellular Biochemistry
Marie Donaldson, Joshua L Owen, Young K Chae, Jennifer N Choi
Immune checkpoint inhibitors targeting the programmed cell death receptor 1 (PD-1) are increasingly used to treat several malignancies, with the most common adverse event being cutaneous toxicity. We report the case of a 68-years-old man with stage IV non-small cell lung cancer treated with nivolumab who developed a pruritic, lichenoid eruption refractory to treatment with topical or systemic steroids, who was started on narrow band ultraviolet B therapy which resolved the reaction.
2018: Frontiers in Oncology
Hideki Ujiie, Lili Ding, Rong Fan, Tatsuya Kato, Daiyoon Lee, Kosuke Fujino, Tomonari Kinoshita, Chang Young Lee, Thomas K Waddell, Shaf Keshavjee, Brian C Wilson, Gang Zheng, Juan Chen, Kazuhiro Yasufuku
BACKGROUND: We have developed ultra-small porphyrin-lipoprotein nanoparticles (<20nm) called "porphyrinHDL" that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells, as a first step towards development of a minimally-invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer...
October 11, 2018: Annals of Thoracic Surgery
Abhishesh Kumar Mehata, Shreekant Bharti, Priya Singh, Matte Kasi Viswanadh, Lakshmi Kumari, Poornima Agrawal, Sanjay Singh, Biplob Koch, Madaswamy S Muthu
Breast cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) has led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted as well as targeted nanoparticles were in the range of 126-186 nm and 74-78% respectively. In-vitro studies on SK-BR-3 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional formulation i...
October 4, 2018: Colloids and Surfaces. B, Biointerfaces
Jordan A Torok, Patrick Oh, Katherine D Castle, Michael Reinsvold, Yan Ma, Lixia Luo, Chang-Lung Lee, David G Kirsch
Stereotactic body radiation therapy is utilized to treat lung cancer. The mechanism of tumor response to high dose RT (HDRT) is controversial, with competing hypotheses of increased direct tumor cell killing vs indirect effects on stroma including endothelial cells. Here we used dual recombinase technology in a primary murine lung cancer model to test whether tumor cells or endothelial cells are critical HDRT targets. Lenti-Cre deleted one or two copies of Atm (KPAFL/+ or KPAFL/FL), whereas adeno-FlpO infected mice expressed Cre in endothelial cells to delete one or both copies of Atm (KPVAFL/+ or KPVAFL/FL) to modify tumor cell or endothelial cell radiosensitivity, respectively...
October 12, 2018: Cancer Research
Weijing Yang, Yaohua Wei, Liang Yang, Jian Zhang, Zhiyuan Zhong, Gert Storm, Fenghua Meng
The clinical use of protein therapeutics with intracellular targets is hampered by its in vivo fragility and low cell permeability. Here, we report that cell-selective penetrating and reduction-responsive polymersomes (CPRPs) mediate high-efficiency targeted delivery of granzyme B (GrB) to orthotopic human lung tumor in vivo. Model protein studies using FITC-labeled cytochrome C (FITC-CC) revealed efficient and high protein loading up to 17.2 wt% for CPRPs. FITC-CC-loaded CPRPs exhibited a small size of 82-90 nm, reduction-responsive protein release, as well as greatly enhanced internalization and cytoplasmic protein release in A549 lung cancer cells compared with the non-targeted FITC-CC-loaded RPs control...
October 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jiale Wang, Tamara Mirzapoiazova, Yi-Hung Carol Tan, Ka Ming Pang, Alex Pozhitkov, Yingyu Wang, Yang Wang, Bolot Mambetsariev, Edward Wang, Mohd W Nasser, Surinder K Batra, Dan Raz, Karen Reckamp, Prakash Kulkarni, Yanfang Zheng, Ravi Salgia
The receptor tyrosine kinase MET is frequently involved in malignant transformation and inhibiting its activity in MET-dependent cancers is associated with improved clinical outcomes. Emerging evidence also suggests that mitochondria play an essential role in tumorigenesis and Dynamin Related Protein (DRP1), a key component of the mitochondrial fission machinery, has emerged as an attractive therapeutic target. Here, we report that inhibiting MET activity with the tyrosine kinase inhibitor MGCD516 attenuates viability, migration, and invasion of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) cell lines in vitro, and significantly retards tumor growth in vivo...
October 12, 2018: Cancer Biology & Therapy
Butuo Li, Cheng Li, Meiying Guo, Shuheng Shang, Xiaogang Li, Peng Xie, Xindong Sun, Jinming Yu, Linlin Wang
Background: The combination of bevacizumab and chemotherapy is still one of the standard treatments for advanced non-small-cell lung cancer (NSCLC) patients in the new era of targeted therapy. Although a high level of baseline lactate dehydrogenase (LDH) was found to predict survival benefit from bevacizumab in patients with metastatic colorectal cancer, the predictive value of serum level of LDH in NSCLC patients treated with bevacizumab has not been investigated yet. Moreover, dynamic evaluation of serum level of LDH changes may be more informative and promising in predicting patients' prognosis...
2018: OncoTargets and Therapy
Sung Joon Kim, Jeong Won Lee, Min Kyu Kang, Jae-Chul Kim, Jeong Eun Lee, Shin-Hyung Park, Mi Young Kim, Seoung-Jun Lee, Soo-Ho Moon, Byoung-Soo Ko
PURPOSE: A hybrid-dynamic conformal arc therapy (HDCAT) technique consisting of a single half-rotated dynamic conformal arc beam and static field-in-field beams in two directions was designed and evaluated in terms of dosimetric benefits for radiotherapy of lung cancer. Materials and METHODS: This planning study was performed in 20 lung cancer cases treated with the VERO system (BrainLAB AG, Feldkirchen, Germany). Dosimetric parameters of HDCAT plans were compared with those of three-dimensional conformal radiotherapy (3D-CRT) plans in terms of target volume coverage, dose conformity, and sparing of organs at risk...
September 2018: Radiation Oncology Journal
Yichao Chen, Jingjing Sun, Yixian Huang, Yanhua Liu, Lei Liang, Da Yang, Binfeng Lu, Song Li
Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36γ plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded with Dox only...
October 8, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Weimin Yin, Xiaolu Yu, Xuejia Kang, Yuge Zhao, Pengfei Zhao, Hongyue Jin, Xuhong Fu, Yakun Wan, Chengyuan Peng, Yongzhuo Huang
Precision medicine has made a significant breakthrough in the past decade. The most representative success is the molecular targeting therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small-cell lung cancer (NSCLC) with oncogenic drivers, approved by the US Food and Drug Administration (FDA) as first-line therapeutics for substituting chemotherapy. However, the rapidly developed TKI resistance invariably leads to unsustainable treatment. For example, gefitinib is the first choice for advanced NSCLC with EGFR mutation, but most patients would soon develop secondary EGFRT790M mutation and acquire gefitinib resistance...
October 11, 2018: Small
Naiquan Mao, Zhiling Liao, Junwei Wu, Kai Liang, Shoufeng Wang, Shaomian Qin, Ying Dou, Hanqing Lin, Xiaowei Dong
NUT carcinoma (NC) is an aggressive squamous tumor characterized by NUT gene rearrangement, and the most common fusion form is BRD4-NUT. However, NC diagnosis is difficult for its rareness and often being confused with a variety of poorly differentiated tumors. A 21-year-old Chinese woman was referred to our hospital for cough and intermittent fever. Chest computed tomography (CT) imaging revealed a left lobe hilar mass. Fiberoptic bronchoscopy results showed that tumor cells were poorly differentiated. In combination with immunohistochemistry staining, she was misdiagnosed with Ewing's sarcoma/primitive neuroectodermal tumor...
October 11, 2018: Cancer Biology & Therapy
Norikazu Matsuo, Koichi Azuma, Satoshi Hattori, Junya Ohtake, Akihiko Kawahara, Hidenobu Ishii, Takaaki Tokito, Kazuhiko Yamada, Yuji Shibata, Tadasuke Shimokawaji, Tetsuro Kondo, Terufumi Kato, Haruhiro Saito, Kouzo Yamada, Tetsuro Sasada, Tomoaki Hoshino
Although programmed death (PD)-1 immune checkpoint therapies target the immune system, the relationship between inflammatory factors and the clinical outcome of anti-PD-1 therapy for non-small cell lung cancer (NSCLC) is not fully understood. Here we examined the association between soluble immune mediators and the outcome of treatment with PD-1 inhibitors in patients with advanced/recurrent NSCLC. In two independent cohorts, we assessed the levels of 88 different soluble immune mediators in peripheral blood before and after anti-PD-1 treatment, and evaluated their associations with clinical outcomes...
October 11, 2018: International Journal of Cancer. Journal International du Cancer
An Qin, David Gersten, Jian Liang, Qiang Liu, Inga Grill, Thomas Guerrero, Craig Stevens, Di Yan
To monitor delivered dose and trigger plan adaptation when deviation becomes unacceptable, a clinical treatment dose (Tx-Dose) reconstruction system based on three-dimensional (3D)/four-dimensional (4D)-cone beam computed tomograpy (CBCT) images was developed and evaluated on various treatment sites, particularly for lung cancer patient treated by stereotactic body radiation therapy (SBRT). This system integrates with our treatment planning system (TPS), Linacs recording and verification system (R&V), and CBCT imaging system, consisting of three modules: Treatment Schedule Monitoring module (TSM), pseudo-CT Generating module (PCG), and Treatment Dose Reconstruction/evaluation module (TDR)...
October 10, 2018: Journal of Applied Clinical Medical Physics
Yibo Yin, Alina C Boesteanu, Zev A Binder, Chong Xu, Reiss A Reid, Jesse L Rodriguez, Danielle R Cook, Radhika Thokala, Kristin Blouch, Bevin McGettigan-Croce, Logan Zhang, Christoph Konradt, Alexandria P Cogdill, M Kazim Panjwani, Shuguang Jiang, Denis Migliorini, Nadia Dahmane, Avery D Posey, Carl H June, Nicola J Mason, Zhiguo Lin, Donald M O'Rourke, Laura A Johnson
We generated two humanized interleukin-13 receptor α2 (IL-13Rα2) chimeric antigen receptors (CARs), Hu07BBz and Hu08BBz, that recognized human IL-13Rα2, but not IL-13Rα1. Hu08BBz also recognized canine IL-13Rα2. Both of these CAR T cell constructs demonstrated superior tumor inhibitory effects in a subcutaneous xenograft model of human glioma compared with a humanized EGFRvIII CAR T construct used in a recent phase 1 clinical trial ( NCT02209376). The Hu08BBz demonstrated a 75% reduction in orthotopic tumor growth using low-dose CAR T cell infusion...
December 21, 2018: Molecular Therapy Oncolytics
Jan Norum, Carsten Nieder
Background: Programmed death ligand 1 (PD-L1) targeting immunotherapies, as pembrolizumab and nivolumab, have significantly improved outcome in patients with non-small cell lung cancer (NSCLC). Tobacco smoking is the number one risk factor for lung cancer and is linked to 80%-90% of these cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcome. We aimed to review the knowledge in immunotherapy. Patients and methods: A systematic review was done...
2018: ESMO Open
Kendall F Moseley, Jarushka Naidoo, Clifton O Bingham, Michael A Carducci, Patrick M Forde, Geoffrey T Gibney, Evan J Lipson, Ami A Shah, William H Sharfman, Laura C Cappelli
BACKGROUND: The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described. CASE PRESENTATIONS: In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both...
October 11, 2018: Journal for Immunotherapy of Cancer
Kimio Yonesaka, Naoki Takegawa, Satomi Watanabe, Koji Haratani, Hisato Kawakami, Kazuko Sakai, Yasutaka Chiba, Naoyuki Maeda, Takashi Kagari, Kenji Hirotani, Kazuto Nishio, Kazuhiko Nakagawa
EGFR tyrosine kinase inhibitors (TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC); however, these tumours eventually acquire chemoresistance. U3-1402 is an anti-HER3 antibody-drug conjugate with a novel topoisomerase I inhibitor, DXd. In the current study, we evaluated the anticancer efficacy of U3-1402 in EGFR-mutant NSCLC cells with acquired resistance to EGFR-TKIs. HCC827GR5 and PC9AZDR7 are EGFR-TKI-resistant clones for gefitinib and osimertinib, respectively. U3-1402 alone or in combination with the EGFR-TKI erlotinib demonstrated potent anticancer efficacy in HCC827GR5 cells using an in vitro growth inhibition assay and in vivo xenograft mouse model...
October 9, 2018: Oncogene
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