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Platinum chemotherapy 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/28291545/adding-bevacizumab-to-single-agent-chemotherapy-for-the-treatment-of-platinum-resistant-recurrent-ovarian-cancer-a-cost-effectiveness-analysis-of-the-aurelia-trial
#4
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/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
#5
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
#6
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/28274569/predictive-value-of-circulating-tumor-cells-ctcs-captured-by-microfluidic-device-in-patients-with-epithelial-ovarian-cancer
#7
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
#8
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
#9
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
#10
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/28259951/sox2-inhibits-wnt-%C3%AE-catenin-signaling-and-metastatic-potency-of-cisplatin-resistant-lung-adenocarcinoma-cells
#11
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
#12
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
https://www.readbyqxmd.com/read/28251557/establishment-and-characterization-of-a-platinum-and-paclitaxel-resistant-high-grade-serous-ovarian-carcinoma-cell-line
#13
Pang-Ning Teng, Nicholas W Bateman, Guisong Wang, Tracy Litzi, Brian E Blanton, Brian L Hood, Kelly A Conrads, Wei Ao, Kate E Oliver, Kathleen M Darcy, William P McGuire, Keren Paz, David Sidransky, Chad A Hamilton, G Larry Maxwell, Thomas P Conrads
High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy...
March 1, 2017: Human Cell
https://www.readbyqxmd.com/read/28240171/effective-strategies-and-applications-of-dendrimers-in-the-treatment-of-ovarian-cancer
#14
Akila Kesavan, Pakala Suresh Babu, Rayala Suresh Kumar, Ganesh Venkatraman
Ovarian cancer, the worldwide leading cause of gynecological cancer-related death, is primarily treated by surgery followed by platinum chemotherapy. Though the tumor initially responds to the treatment, only 30% of 5 year survival period has been recorded and this is mainly attributed to the acquired chemo resistance and frequent recurrence of tumor. Combination chemotherapy as well, led to therapeutic failure due to non-specificity and subsequent side effects. However, polymer mediated drug delivery aids in overcoming these impediments...
February 23, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28238563/the-development-and-use-of-vascular-targeted-therapy-in-ovarian-cancer
#15
REVIEW
Dana M Chase, David J Chaplin, Bradley J Monk
Combination vascular-targeted therapies (VTTs) represent a promising approach for patients with platinum-resistant recurrent ovarian cancer (OC). VTTs include two mechanistically distinct classes of agents: anti-angiogenic agents (AAs) and vascular-disrupting agents (VDAs). AAs suppress growth of new tumor vasculature through inhibition of vascular endothelial growth factor (VEGF) and other pro-angiogenic molecules. Bevacizumab, a monoclonal antibody that binds to VEGF, has improved progression-free survival (PFS) when given with chemotherapy in patients with advanced OC...
February 24, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#16
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28215839/unraveling-the-etiology-of-ovarian-cancer-racial-disparity-in-the-deep-south-is-it-nature-or-nurture
#17
Jerlinda Ross, Katelyn V Braswell, Luciana Madeira da Silva, Frances Mujica, Sam Stutsman, Michael A Finan, William Nicolson, Mary Danner Harmon, Megan Missanelli, Alex Cohen, Ajay Singh, Jennifer M Scalici, Rodney P Rocconi
BACKGROUND: Our objective was to evaluate racial treatment and survival disparities in black women with ovarian cancer in the Deep South and to determine how environmental factors / socioeconomic status (SES) influence survival. METHODS: A retrospective study of ovarian cancer patients from 2007 to 2014 was performed. Socioeconomic status (SES) was obtained though U.S. Census block data and compared using Yost scores. Comparisons were performed using standard statistical approaches...
February 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28215024/pharmacogenomics-of-platinum-based-chemotherapy-in-non-small-cell-lung-cancer-focusing-on-dna-repair-systems
#18
REVIEW
Yi Xiong, Bi-Yun Huang, Ji-Ye Yin
Drug therapy for non-small cell lung cancer consists mainly of platinum-based chemotherapy regimens. However, toxicity, drug resistance, and high risk of death have been seen in the clinic, which means there is a need for optimizing the use of medications. Platinum resistance could be mediated by a series of DNA repair pathways, and therefore, these pathways should be taken into account for optimizing drug using. The goal of pharmacogenomics is to elucidate genetic factors, such as DNA repair genes, which might underlie drug efficacy and effectiveness, and to improve therapeutic effects or guide personalized therapy as well...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28206967/calcium-regulatory-proteins-as-modulators-of-chemotherapy-in-human-neuroblastoma
#19
Ana-Maria Florea, Elizabeth Varghese, Jennifer E McCallum, Safa Mahgoub, Irfan Helmy, Sharon Varghese, Neha Gopinath, Steffen Sass, Fabian J Theis, Guido Reifenberger, Dietrich Büsselberg
Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i)...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#20
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
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