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Platinum resistance

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https://www.readbyqxmd.com/read/28325254/egfr-inhibition-in-nsclc-new-findings%C3%A2-and-opened-questions
#1
REVIEW
Francesco Passiglia, Angela Listì, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Viviana Bazan, Antonio Russo
The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients' outcomes...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325092/effectiveness-of-low-dose-oral-etoposide-treatment-in-patients-with-recurrent-and-platinum-resistant-epithelial-ovarian-cancer
#2
Yakup Bozkaya, Mutlu Doğan, Gökmen Umut Erdem, Gökhan Tulunay, Hikmet Uncu, Zafer Arık, Umut Demirci, Ozan Yazıcı, Nurullah Zengin
The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment...
March 21, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#3
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319063/compromised-brca1-palb2-interaction-is-associated-with-breast-cancer-risk
#4
T K Foo, M Tischkowitz, S Simhadri, T Boshari, N Zayed, K A Burke, S H Berman, P Blecua, N Riaz, Y Huo, Y C Ding, S L Neuhausen, B Weigelt, J S Reis-Filho, W D Foulkes, B Xia
The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319033/characterization-of-hierarchical-%C3%AE-moo-sub-3-sub-plates-toward-resistive-heating-synthesis-electrochemical-activity-of-%C3%AE-moo-sub-3-sub-pt-modified-electrode-toward-methanol-oxidation-in-neutral-ph
#5
Emanuela Filippo, Francesca Baldassarre, Marco Tepore, Maria Rachele Guascito, Daniela Chirizzi, Antonio Tepore
The growth of MoO<sub>3</sub> hierarchical plates was obtained by direct resistive heating of molybdenum foil at ambient pressure in absence of any catalysts and templates. Plates synthesized after 60 min resistive heating typically growth in an single-crystalline orthorhombic structure that develop preferentially in [001] direction, as characterized by HRTEM, SAD and Raman-scattering measurements. They are about 100-200nm in thickness and a few tens micrometers in length. As heating time proceeds to 80 min, plates of α-MoO<sub>3</sub> form a branched structure...
March 20, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28294554/sequential-functionalization-of-a-natural-crosslinker-leads-to-designer-silicone-networks
#6
Scott E Laengert, Alyssa F Schneider, Yang Chen, Michael A Brook
Precise silicone networks are difficult to prepare from multiple starting materials because of poor special control over crosslink location, competing side reactions, and incompatible catalysts among other reasons. We demonstrate that cure processes catalyzed by B(C6F5)3 (the Piers-Rubinsztajn reaction) and platinum-catalyzed hydrosilylation are perfectly compatible, and can be used in either order. It is possible to perform three different, selective, sequential reactions in the same pot using H-terminated silicones as chain extenders in all cases to give explicit networks...
March 10, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28291774/brca2-secondary-mutation-mediated-resistance-to-platinum-and-parp-inhibitor-based-therapy-in-pancreatic-cancer
#7
Michael J Pishvaian, Andrew V Biankin, Peter Bailey, David K Chang, Daniel Laheru, Christopher L Wolfgang, Jonathan R Brody
BACKGROUND: Pancreatic cancer has become the third leading cause of cancer death with minimal improvements in outcome for over 40 years. Recent trials of therapies that target-defective DNA maintenance using poly (ADP-ribose) polymerase (PARP) inhibitors are showing promising results, yet invariably patients recur and succumb to disease. Mechanisms of resistance to platinum-based and PARP inhibitor therapy in other cancer types include secondary mutations, which restore the integrity of DNA repair through an increasing number of different mechanisms...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28291545/adding-bevacizumab-to-single-agent-chemotherapy-for-the-treatment-of-platinum-resistant-recurrent-ovarian-cancer-a-cost-effectiveness-analysis-of-the-aurelia-trial
#8
Weiya Z Wysham, Elisabeth M Schaffer, Theresa Coles, Dario R Roque, Stephanie B Wheeler, Kenneth H Kim
OBJECTIVE: AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. METHODS: A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial...
March 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28290714/polymeric-micelles-for-targeted-tumor-therapy-of-platinum-anticancer-drugs
#9
Yuki Mochida, Horacio Cabral, Kazunori Kataoka
Platinum anticancer drugs are effective against a wide range of tumors, though their severe adverse effects and resistance remain unresolved. A breakthrough in these drawbacks could be achieved by using polymeric micelles, i.e. nanoassemblies having a drug loaded core and a protective hydrophilic shell, incorporating platinum drugs for tumor-targeted delivery. Areas covered: The development of cisplatin- (NC-6004) and DACHPt-loaded micelles (NC-4016) has been reviewed, particularly, from the viewpoint of the effect of their structural features on the tumor-targeting efficacy...
March 14, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28288821/reversal-of-cisplatin-resistance-in-human-gastric-cancer-cells-by-a-wogonin-conjugated-pt-iv-prodrug-via-attenuating-casein-kinase-2-mediated-nuclear-factor-%C3%AE%C2%BAb-pathways
#10
Feihong Chen, Xiaodong Qin, Gang Xu, Shaohua Gou, Xiufeng Jin
Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity. While, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28285694/sbrt-for-oligoprogressive-oncogene-addicted-nsclc
#11
REVIEW
L Basler, S G C Kroeze, M Guckenberger
Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. Despite initial activity of the TKIs, ultimately all patients present with disease progression after about a year on TKI therapy due to resistance development...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28276682/anticancer-platinum-iv-prodrugs-containing-mono-aminophosphonate-ester-as-a-targeting-group-inhibit-matrix-metalloproteinases-and-reverse-multidrug-resistance
#12
Xiaochao Huang, Rizhen Huang, Shaohua Gou, Zhimei Wang, Heng-Shan Wang
A novel class of platinum(IV) complexes comprising a mono-aminophosphonate ester moiety, which can not only act as a bone-targeting group but also inhibit matrix metalloproteinases (MMPs), were designed and synthesized. Biological assay of these compounds showed that they had potent antitumor activities against the tested cancer cell lines compared with cisplatin and oxaliplatin and indicated low cytotoxicity to human normal liver cells. Particularly, the platinum(IV) complexes were much sensitive to cisplatin resistant cancer cell lines...
March 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28274569/predictive-value-of-circulating-tumor-cells-ctcs-captured-by-microfluidic-device-in-patients-with-epithelial-ovarian-cancer
#13
Maria Lee, Eun Jae Kim, Youngnam Cho, Sunshin Kim, Hyun Hoon Chung, Noh Hyun Park, Yong-Sang Song
OBJECTIVE: To test an electrically conductive chip, incorporating a nanoroughened microfluidic platform for the capture of circulating tumor cells (CTCs), and assess its clinical merit in instances of epithelial ovarian cancer (EOC). METHODS: A total of 54 patients with EOC recruited between August 2014 and May 2015 were enrolled in this prospective study. CTCs in peripheral blood were detected in advance of primary tumor resection and before initiating adjuvant chemotherapy for recurrent disease...
March 5, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28273485/clinical-factors-of-response-in-patients-with-advanced-ovarian-cancer-participating-in-early-phase-clinical-trials
#14
Angela George, Rebecca Kristeleit, Saeed Rafii, Caroline O Michie, Rebecca Bowen, Vasiliki Michalarea, Tom van Hagen, Mabel Wong, Grigorios Rallis, L Rhoda Molife, Juanita Lopez, Udai Banerji, Susana N Banerjee, Martin E Gore, Johann S de Bono, Stan B Kaye, Timothy A Yap
Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010...
March 5, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28270299/research-advances-in-resistance-to-platinum-based-chemotherapy-in-lung-cancer
#15
Yajuan Zhang, De Chang, Jianpeng Zhang
Platinum-based chemotherapy is the the cornerstone of treatment of many cancers. Combinations of platinum drugs with other agents are still the mainstream therapies for non-small cell lung cancer,showing significant effectiveness in an early phase. Along with the treatment,the tumor cells can become resistant to chemotherapy drugs,which affect the efficacy and prognosis. The mechanisms of drug resistance are complicated,including abnormal expressions of membrane proteins,enhanced DNA repair functions,abnormal regulation mechanisms of apoptosis,and enhanced cellular detoxification function...
February 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28263384/mesothelium-expression-of-vascular-cell-adhesion-molecule-1-vcam-1-is-associated-with-an-unfavorable-prognosis-in-epithelial-ovarian-cancer-eoc
#16
Jennifer M Scalici, Sanja Arapovic, Erin J Saks, Kristen A Atkins, Gina Petroni, Linda R Duska, Jill K Slack-Davis
BACKGROUND: Mesothelium vascular cell adhesion molecule-1 (VCAM-1) expression in the metastatic epithelial ovarian cancer (EOC) microenvironment is induced by tumor and mediates tumor cell invasion. VCAM-1 imaging suggests expression during treatment is an indicator of platinum resistance. Here, we assess the potential prognostic significance of mesothelium VCAM-1 expression and prospectively evaluate whether soluble VCAM-1 (sVCAM-1) is a surrogate for mesothelium expression. METHODS: A retrospective review of EOC patients was performed to evaluate outcomes with mesothelium VCAM-1 expression determined by immunohistochemistry of peritoneum or omentum specimens...
May 15, 2017: Cancer
https://www.readbyqxmd.com/read/28263086/the-potential-of-combi-molecules-with-dna-damaging-function-as-anticancer-agents
#17
Guohui Sun, Tengjiao Fan, Lijiao Zhao, Yue Zhou, Rugang Zhong
DNA-damaging agents, such as methylating agents, chloroethylating agents and platinum-based agents, have been extensively used as anticancer drugs. However, the side effects, high toxicity, lack of selectivity and resistance severely limit their clinical applications. In recent years, a strategy combining a DNA-damaging agent with a bioactive molecule (e.g., enzyme inhibitors) or carrier (e.g., steroid hormone and DNA intercalators) to produce a new 'combi-molecule' with improved efficacy or selectivity has been attempted to overcome these drawbacks...
March 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28260069/chemosensitizing-effect-of-shrna-mediated-ercc1-silencing-on-a-xuanwei-lung-adenocarcinoma-cell-line-and-its-clinical-significance
#18
Weiwei Wang, Lijun Zhang, Liang Liu, Yongfa Zheng, Yong Zhang, Siyuan Yang, Rongliang Shi, Shaojia Wang
Lung cancer is a common fatal malignancy in both men and women. Xuanwei, Yunnan has the highest incidence of lung cancer in China. The area has a specific risk factor in the domestic combustion of bituminous coal, and lung cancer patients from this area tend to be resistant to platinum-based treatments. However, little is known about the mechanism of platinum resistance in patients from Xuanwei. Herein, we used lentiviral infection with shRNA to silence expression of the DNA repair enzyme ERCC1 in XWLC05 both in its RNA and protein expression level, a lung adenoma cell line derived from a patient from Xuanwei...
February 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259951/sox2-inhibits-wnt-%C3%AE-catenin-signaling-and-metastatic-potency-of-cisplatin-resistant-lung-adenocarcinoma-cells
#19
Jinxi He, Juan Shi, Kangjian Zhang, Jing Xue, Jing Li, Jiali Yang, Juan Chen, Jun Wei, Hong Ren, Xiaoming Liu
Lung cancer remains one of the most common cancer-associated mortalities worldwide, and platinum-based doublet chemotherapies are recommended as the first‑line treatment for advanced non‑small cell lung cancer (NSCLC). However, the frequent development of multidrug resistance, to cisplatin regimens in particular, is a major cause of chemotherapy failure in patients with aggressive NSCLC. Wnt/β‑catenin signaling and sex‑determining region Y box 2 (Sox2) have been implicated in the development and progression and resistance to epidermal growth factor receptor‑targeting therapy in lung cancer...
February 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258670/the-role-of-metallothionein-in-oncogenesis-and-cancer-treatment
#20
Anna Bizoń, Kinga Jędryczko, Halina Milnerowicz
Metallothionein is cysteine-rich low molecular mass protein. The involvement of MT in many physiological and pathophysiological processes such as apoptosis, proliferation, angiogenesis, and the detoxification of heavy metals suggested participation of this protein in carcinogenesis and tumor therapy. Depending on the type of tissue and classification of carcinoma various it was observed relation between MT expression and tumor type, stage, grade, poor prognosis and body resistance to radiotherapy and chemotherapy...
February 14, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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