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Targeted therapies lung cancer

Wei-Hsun Hsu, Xiaoliang Zhao, Jianquan Zhu, In-Kyu Kim, Guanhua Rao, Justine McCutcheon, Shuo-Tse Hsu, Beverly Teicher, Bhaskar Kallakury, Afshin Dowlati, Yu-Wen Zhang, Giuseppe Giaccone
INTRODUCTION: Platinum-based chemotherapy remains the standard treatment for patients with small cell lung cancer (SCLC), but the benefit of the treatment is often hampered by rapid development of drug resistance. Thus far, there is no targeted therapy available for SCLC. Over 90% of SCLC tumors harbor mutations in the tumor suppressor gene p53, an important DNA damage checkpoint regulator, and these tumor cells rely predominantly on the checkpoint kinases to control DNA damage response...
February 13, 2019: Journal of Thoracic Oncology
Jong Woo Lee, Yu Zhang, Kyung Jin Eoh, Roshan Sharma, Miguel F Sanmamed, Jenny Wu, Justin Choi, Hee Sun Park, Akiko Iwasaki, Edward Kaftan, Lieping Chen, Vali Papadimitrakopoulou, Roy S Herbst, Ja Seok Koo
PURPOSE: To characterize the tumor-infiltrating immune cells population in Kras/p53-driven lung tumors and to evaluate the combinatorial anti-tumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed cell death protein-1 (PD-1) or programmed cell death protein ligand 1 (PD-L1) in vivo. EXPERIMENTAL DESIGN: Trp53FloxFlox ;KrasG12D/+ ;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were utilized to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase...
February 13, 2019: Journal of Thoracic Oncology
Arrvind Raghunath, Kunal Desai, Manmeet S Ahluwalia
In the past, the standard of care for treatment of BM was whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. There has been a greater role for medical therapies in the last two decades due to the discovery of driver mutations and corresponding targeted therapies. These innovations have dramatically altered the approach to treating these patients. Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma...
February 15, 2019: Current Treatment Options in Oncology
Jeong-Hwa Baek, Hong Shik Yun, Gyoo Taik Kwon, Janet Lee, Ju-Young Kim, Yunhui Jo, Jae-Min Cho, Chang-Woo Lee, Jie-Young Song, Jiyeon Ahn, Jae-Sung Kim, Eun Ho Kim, Sang-Gu Hwang
Current lung cancer treatments are far from satisfactory; thus, finding novel treatment targets is crucial. We recently identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), which is involved in fibrosis and tissue remodeling as a radioresistance-related protein in lung cancer cells; however, its mechanism is unclear. In this study, we designed human PLOD3-specific short interfering (si)RNAs and tested their effects on tumor growth inhibition in vitro and in vivo. PLOD3 knockdown overcame chemoresistance and decreased radioresistance by inducing caspase-3-dependent apoptosis in lung cancer cells...
February 15, 2019: Cell Death & Disease
Carsten Nieder, Matthias Guckenberger, Laurie E Gaspar, Chad G Rusthoven, Dirk De Ruysscher, Arjun Sahgal, Timothy Nguyen, Anca L Grosu, Minesh P Mehta
BACKGROUND: Different management options exist for patients with brain metastases from non-small cell lung cancer (NSCLC), patients whose treatment with whole brain radiotherapy (WBRT) has become more controversial over the last decade. It is not trivial to find the optimal balance of over- versus undertreatment in these patients. Several recent trials, including the randomized QUARTZ trial now influence the decision to recommend or withhold WBRT for patients with unfavorable prognosis, and similarly, for favorable prognosis patients, the balance between radiosurgery alone or WBRT has become a nuanced decision...
February 15, 2019: Radiation Oncology
Jacqueline L Olin, Olga Klibanov, Alexandre Chan, Linda M Spooner
OBJECTIVE: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. DATA SOURCES: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. STUDY SELECTION AND DATA EXTRACTION: Article bibliographies and drug interaction databases were reviewed...
February 15, 2019: Annals of Pharmacotherapy
Yusuf A Haggag, Kyle B Matchett, Robert A Falconer, Mohammad Isreb, Jason Jones, Ahmed Faheem, Paul McCarron, Mohamed El-Tanani
The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (NPs)...
February 14, 2019: Cancers
Kumar Prabhash
The management of advanced nonsmall cell lung cancer (NSCLC) patients is becoming increasingly complex with the identification of driver mutations/rearrangements and development/availability of appropriate targeted therapies. In 2017, an expert group of medical oncologists with expertise in treating lung cancer used data from published literature and experience to arrive at practical consensus recommendations on treatment of advanced NSCLC for use by the community oncologists. This was published subsequently in the Indian Journal of Cancer with a plan to be updated annually...
January 2019: South Asian Journal of Cancer
Xusheng Wang, Haiyan Chen, Xiaowei Zeng, Wenpeng Guo, Yu Jin, Shan Wang, Ruiyun Tian, Yanjiang Han, Ling Guo, Jimin Han, Yaojiong Wu, Lin Mei
Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered via MSC accumulated in the lung...
January 2019: Acta Pharmaceutica Sinica. B
Eun Hye Lee, Eun Young Kim, Sang Hoon Lee, Yun Ho Roh, Ah Young Leem, Joo Han Song, Song Yee Kim, Kyung Soo Chung, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Joon Chang, Moo Suk Park
Solid malignancies are associated with the development of Pneumocystis jirovecii pneumonia (PJP). This study aimed to evaluate the risk factors for PJP among patients with lung cancer. This retrospective case-control study compared patients who had lung cancer with PJP (n = 112) or without PJP (n = 336) matched according to age, sex, histopathology, and stage. PJP definition was based on (i) positive PCR or direct immunofluorescence results for pneumocystis, (ii) clinical symptoms and radiological abnormalities that were consistent with a pneumonic process, and (iii) received targeted PJP treatment...
February 14, 2019: Scientific Reports
Marcel P Trefny, Sacha I Rothschild, Franziska Uhlenbrock, Dietmar Rieder, Benjamin Kasenda, Michal A Stanczak, Fiamma Berner, Abhishek S Kashyap, Monika Kaiser, Petra Herzig, Severin Poechtrager, Daniela S Thommen, Florian Geier, Spasenija Savic, Philip Jermann, Ilaria Alborelli, Stefan Schaub, Frank Stenner, Martin Früh, Zlatko Trajanoski, Lukas Flatz, Kirsten D Mertz, Alfred Zippelius, Heinz Läubli
PURPOSE: PD-(L)1 blocking antibodies have clinical activity in metastatic non-small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade.Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathways. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells were collected from 35 NSCLC patients receiving nivolumab monotherapy...
February 14, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nauman S Chaudhry, Wenya Linda Bi, Saksham Gupta, Abhishek Keraliya, Naomi Shimizu, E Antonio Chiocca
BACKGROUND: Pneumoperitoneum after surgical manipulation of the abdomen implies a perforation. Rare cases of non-operated cancer patients, largely with gastrointestinal or genitourinary cancers, have been noted to have radiological findings of pneumatosis intestinalis and/or pneumoperitoneum as a complication of molecular-targeted therapy (MTT) without confounding factors for perforation. We present a patient with a cranial malignancy treated with bevacizumab who subsequently manifested with pneumatosis intestinalis...
February 11, 2019: World Neurosurgery
Stefan Zimmerman, Arundhati Das, Shuhang Wang, Ricklie Julian, Leena Gandhi, Juergen Wolf
Small cell lung cancer remains an aggressive, deadly cancer with only modest effect on survival from standard chemotherapy. However, with the advent of immunotherapy and comprehensive genomic and transcriptomic profiling, multiple new targets are showing promise in the clinical arena, and just recently PD-L1 inhibition has been shown to improve the efficacy of standard chemotherapy in extended disease SCLC. Our increasing understanding of the interactions between different pathways will enable more tailored immuno- as well as targeted therapies based on specific biomarkers and rational combinations...
February 11, 2019: Journal of Thoracic Oncology
Vaishali Kapoor, Abhay Kumar Singh, Buck E Rogers, Dinesh Thotala, Dennis E Hallahan
Targeted molecular imaging allows specific visualization and monitoring of tumors. Cancer-specific peptides have been developed for imaging and therapy. Peptides that specifically target cancer have several advantages including, ease of synthesis, low antigenicity, and enhanced diffusion into tissues. We developed the HVGGSSV peptide as a molecular targeting/imaging agent. HVGGSSV targets Tax interacting protein 1 (TIP1) which is a 14 kDa PDZ domain-containing protein that is overexpressed in cancer. We docked HVGGSSV in silico using the three-dimensional structure of TIP1 and found the binding energy was -6...
February 11, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Martyna Filipska, Carlos Pedraz-Valdunciel, Imane Chaib, Rafael Rosell
Biological therapies, with immunotherapy leading the field, have arisen as one of the quickest expanding areas of research for cancer treatment in the last few years. The clear benefits for patients are undeniable, satisfying the long-awaited necessity of a target-specific therapy. However, its full potential remains still unexploited due to a lack of response in a majority of patients and pending reliable biomarkers. Areas covered: This review provides a summarizing view of the current biological therapies for lung cancer, focusing on immunotherapy - including immune checkpoint inhibitors, adoptive cell therapy and vaccines available in clinical/pre-clinical settings or currently in development...
February 14, 2019: Expert Opinion on Biological Therapy
Xin Li, Michael Enzerra, Daniel Arnold Smith, Amir Ata Rahnemai-Azar, Elias Kikano, Nikhil H Ramaiya
Until recently, the treatment of small cell lung cancer (SCLC), a malignancy classically described as having a robust response to first-line therapy with near-universal recurrence, has remained relatively unchanged. Advancements in the management of SCLC have lagged behind those seen for non-small cell lung cancers. As the era of precision medicine and targeted immunotherapy evolves, radiologists must be familiar with the modern treatment paradigms of SCLC and associated imaging patterns, including classic and nonclassic appearances of treatment complications...
February 11, 2019: Journal of Computer Assisted Tomography
Jaxon J Vallely, Kathryn E Hudson, Susan C Locke, Steven P Wolf, Gregory P Samsa, Amy P Abernethy, Thomas W LeBlanc
PURPOSE: Pruritus is a common symptom in cutaneous malignancies, but its impact on patients with solid tumors is unclear. We explored the impact and management of pruritus in patients with solid tumors, using patient-reported outcomes (PRO) data from a real-world registry. METHODS: From 2006 to 2011, patients seen in the Duke Cancer Institute reported their symptoms via the Patient Care Monitor v2.0, a validated PRO tool that includes a 0-10-point question about pruritus severity...
February 14, 2019: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Shikha Saini, Lakshmi Sripada, Kiara Tulla, Prabhakaran Kumar, Fei Yue, Nicholas Kunda, Ajay V Maker, Bellur S Prabhakar
Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, explored its effect on cellular proliferation and metastases and examined its therapeutic potential in an orthotopic ATC model in athymic nude mice. When compared to untreated control and scramble siRNA, MADD siRNA treatment inhibited the proliferative capacity of 8505C, C643 and HTH7 cells in vitro and 8505C-derived-orthotopic tumor growth in vivo...
February 13, 2019: Cell Death & Disease
Sunil Singhal, Jason Stadanlick, Michael J Annunziata, Abhishek S Rao, Pratik S Bhojnagarwala, Shaun O'Brien, Edmund K Moon, Edward Cantu, Gwenn Danet-Desnoyers, Hyun-Jeong Ra, Leslie Litzky, Tatiana Akimova, Ulf H Beier, Wayne W Hancock, Steven M Albelda, Evgeniy B Eruslanov
Data from mouse tumor models suggest that tumor-associated monocyte/macrophage lineage cells (MMLCs) dampen antitumor immune responses. However, given the fundamental differences between mice and humans in tumor evolution, genetic heterogeneity, and immunity, the function of MMLCs might be different in human tumors, especially during early stages of disease. Here, we studied MMLCs in early-stage human lung tumors and found that they consist of a mixture of classical tissue monocytes and tumor-associated macrophages (TAMs)...
February 13, 2019: Science Translational Medicine
Leif E Peterson
Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction...
February 12, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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