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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28215024/pharmacogenomics-of-platinum-based-chemotherapy-in-non-small-cell-lung-cancer-focusing-on-dna-repair-systems
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28184025/metabolic-interrogation-as-a-tool-to-optimize-chemotherapeutic-regimens
#4
Vlad C Sandulache, Yunyun Chen, Lei Feng, William N William, Heath D Skinner, Jeffrey N Myers, Raymond E Meyn, Jinzhong Li, Ainiwaer Mijiti, James A Bankson, Clifton D Fuller, Marina Y Konopleva, Stephen Y Lai
Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28183801/fatty-acid-16-4-n-3-stimulates-a-gpr120-induced-signaling-cascade-in-splenic-macrophages-to-promote-chemotherapy-resistance
#5
Julia M Houthuijzen, Ilse Oosterom, Brian D Hudson, Akira Hirasawa, Laura G M Daenen, Chelsea M McLean, Steffen V F Hansen, Marijn T M van Jaarsveld, Daniel S Peeper, Sahar Jafari Sadatmand, Jeanine M L Roodhart, Chris H A van de Lest, Trond Ulven, Kenji Ishihara, Graeme Milligan, Emile E Voest
Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid, 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid), induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts its effect by activating splenic F4/80(+)/CD11b(low) macrophages, which results in production of chemoprotective lysophosphatidylcholines (LPCs). Pharmacologic studies, together with analysis of expression patterns, identified GPR120 on F4/80(+)/CD11b(low) macrophages as the relevant receptor for 16:4(n-3)...
February 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28178720/erbb4-expression-in-ovarian-serous-carcinoma-resistant-to-platinum-based-therapy
#6
Ozlen Saglam, Yin Xiong, Douglas C Marchion, Carolina Strosberg, Robert M Wenham, Joseph J Johnson, Daryoush Saeed-Vafa, Christopher Cubitt, Ardeshir Hakam, Anthony M Magliocco
Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28155621/recent-approaches-to-platinum-iv-prodrugs-a-variety-of-strategies-for-enhanced-delivery-and-efficacy
#7
Anas Najjar, Naeema Rajabi, Rafik Karaman
BACKGROUND: Intensive efforts have been implemented to improve the efficacy of platinum complexes especially with emerging cisplatin resistance and elevated cancer deaths. Platinum(IV) agents show better pharmacokinetics and decreased side effects compared to Platinum(II) agents. METHODS: This review aims to summarize and categorize the strategies being employed to improve the efficacy of Platinum-based anticancer agents in recent years. RESULTS: Nanoparticles and nanoplatforms offer a vast variety of strategies in targeting specific tumor types and delivering one or two lethal drugs simultaneously...
February 1, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28154921/a-phase-1-2a-dose-escalation-safety-pharmacokinetic-and-preliminary-efficacy-study-of-intraperitoneal-administration-of-bc-819-h19-dta-in-subjects-with-recurrent-ovarian-peritoneal-cancer
#8
Ofer Lavie, David Edelman, Tally Levy, Ami Fishman, Ayala Hubert, Yakir Segev, Eli Raveh, Michal Gilon, Avraham Hochberg
BACKGROUND: H19 is a paternally imprinted, oncofetal gene expressed in various embryonic tissues and in 85% of the ovarian tumors. H19-DTA (BC-819) is a DNA plasmid that drives the expression of the diphtheria toxin gene under the regulation of the H19 promoter sequence and therefore is a potential treatment for various tumors that overexpress the H19 gene, among them-ovarian cancer. OBJECTIVE: To assess the safety and efficacy of intra-peritoneal (IP) instillations of H19-DTA (BC-819) plasmid in treating ovarian/peritoneal cancer patients with advanced recurrent disease...
February 3, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28154416/long-noncoding-rna-expression-signature-to-predict-platinum-based-chemotherapeutic-sensitivity-of-ovarian-cancer-patients
#9
Rong Liu, Ying Zeng, Cheng-Fang Zhou, Ying Wang, Xi Li, Zhao-Qian Liu, Xiao-Ping Chen, Wei Zhang, Hong-Hao Zhou
Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150354/tet1-promotes-cisplatin-resistance-via-demethylating-the-vimentin-promoter-in-ovarian-cancer
#10
Xi Han, Yuanyuan Zhou, Yuanyi You, Jiaojiao Lu, Lijie Wang, Huilian Hou, Jing Li, Wei Chen, Le Zhao, Xu Li
The development of chemo-resistance impairs the outcome of the first line platinum-based chemotherapies for ovarian cancer. Deregulation of DNA methylation/demethylation provides a critical mechanism for the occurrence of chemo-resistance. The ten-eleven translocation (TET) family of dioxygenases including TET1/2/3 plays an important part in DNA demethylation, but their roles in cisplatin resistance have not been elucidated. Using cisplatin-sensitive and cisplatin-resistant ovarian cancer cell models, we found that TET1 was significantly upregulated in cisplatin-resistant CP70 cells compared with that in cisplatin-sensitive A2780 cells...
February 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28140689/the-efficacy-of-trabectedin-in-treating-ovarian-cancer
#11
Eleonora Teplinsky, Thomas J Herzog
The majority of women with epithelial ovarian cancer present with advanced stage disease and there is a critical need for novel drugs and treatment strategies to improve outcomes. Trabectedin is a unique cytotoxic agent with a complex mechanism of action. It binds to guanines in the N2 position in the minor groove of DNA and its cytotoxicity involves DNA repair pathways and transcription regulation. Trabectedin's activity is also related to the drug-induced changes of the tumor microenvironment. It has been shown to improve progression-free survival in combination with pegylated liposomal doxorubicin in patients with platinum-sensitive relapsed ovarian cancer...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28131786/buparlisib-and-paclitaxel-in-patients-with-platinum-pretreated-recurrent-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-beril-1-a-randomised-double-blind-placebo-controlled-phase-2-trial
#12
Denis Soulières, Sandrine Faivre, Ricard Mesía, Éva Remenár, Shau-Hsuan Li, Andrey Karpenko, Arunee Dechaphunkul, Sebastian Ochsenreither, Laura Anna Kiss, Jin-Ching Lin, Raj Nagarkar, László Tamás, Sung-Bae Kim, Jozsef Erfán, Anna Alyasova, Stefan Kasper, Carlo Barone, Sabine Turri, Arunava Chakravartty, Marie Chol, Paola Aimone, Samit Hirawat, Lisa Licitra
BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck...
January 25, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28129775/cmtm1_v17-is-associated-with-chemotherapy-resistance-and-poor-prognosis-in-non-small-cell-lung-cancer
#13
Jiahui Si, Panpan Zhang, Dan Tian, Xing Wang, Yuanyuan Ma, Jianzhi Zhang, Lu Wang, Yue Yang
BACKGROUND: Considering neoadjuvant chemotherapy (NAC) prior to surgery could shrink and reduce the primary tumor and distant micro-metastases to reduce the high relapses rates, NAC has been an accepted therapeutic management for patients with non-small cell lung cancer (NSCLC). CMTM1_v17 is highly expressed in human testis tissues and solid tumor tissues but relatively low expression was obtained in the corresponding normal tissues. This study aims to investigate the significance of CMTM1_v17 in NSCLC and its association with platinum-based NAC efficacy...
January 28, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28123908/comparison-of-different-sample-preparation-methods-for-platinum-determination-in-cultured-cells-by-graphite-furnace-atomic-absorption-spectrometry
#14
Man Xiao, Zaiju Huang, Jing Cai, Jinghui Jia, Yuzeng Zhang, Weihong Dong, Zehua Wang
BACKGROUND: Platinum-based agents are widely used in chemotherapy against solid tumors and insufficient intracellular drug accumulation is one of the leading causes of platinum resistance which is associated with poor survival of tumor patients. Thus, the detection of intracellular platinum is pivotal for studies aiming to overcome platinum resistance. In the present study, we aimed to establish a reliable graphite furnace atomic absorption spectrometry (GFAAS)-based assay to quantify the intracellular platinum content for cultured cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28120035/the-role-of-nrf2-and-atf2-in-resistance-to-platinum-based-chemotherapy
#15
Jianli Chen, Charalambos Solomides, Fiona Simpkins, Henry Simpkins
PURPOSE: Nrf2 and its role in controlling levels of the AKR family of aldo-keto reductases which have been implicated in resistance to platinum-based chemotherapy was studied in ovarian, cervical and lung cell lines. METHODS: Nrf2 shRNA knockdowns of cells from different tumor origins were prepared to determine the role of this factor in producing resistance to platinum chemotherapy. RESULTS: Nrf2 knockdowns resulted in marked decreases in AKR1C1, AKR1C2 and to a lesser extent AKR1C3...
January 24, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28118323/chemotherapy-vs-tamoxifen-in-platinum-resistant-ovarian-cancer-a-phase-iii-randomised-multicentre-trial-ovaresist
#16
Kristina Lindemann, Emma Gibbs, Elisabeth Åvall-Lundqvist, Rene dePont Christensen, Kathrine Woie, Marten Kalling, Annika Auranen, Seija Grenman, Thomas Hoegberg, Per Rosenberg, Tone Skeie-Jensen, Elisabet Hjerpe, Anne Dørum, Val Gebski, Gunnar Kristensen
BACKGROUND: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. METHODS: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40 mg daily...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28117012/current-status-and-perspectives-regarding-the-therapeutic-potential-of-targeting-egfr-pathway-by-curcumin-in-lung-cancer
#17
Mojtaba Shafiee, Elham Mohamadzade, Soudabeh ShahidSales, Samaneh Khakpouri, Mina Maftouh, Seyed Alireza Parizadeh, Seyed Mahdi Hasanian, Amir Avan
Lung cancer is among the leading cause of cancer-related-deaths and non-small cell lung cancer (NSCLC) is the most common form of lung cancer. More than 70% of NSCLC patients have locally advanced or metastatic disease at diagnosis, which are then being treated with platinum-based chemotherapy or epidermal-growth-factor-receptor (EGFR) inhibitors in patients harboring activating EGFR-mutations. Several molecules which target multiple ErbB receptors and EGFR, have been developed, including gefitinib and erlotinib, although most of the patients become resistance...
January 23, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28114816/a-case-of-chronic-hypomagnesemia-in-a-cancer-survivor
#18
Marko Velimirovic, Joshua Charles Ziperstein, Andrew Zoltan Fenves
OBJECTIVES: Hypomagnesemia is common among hospitalized patients, particularly those who are critically ill. It can be associated with a number of potentially life-threatening cardiovascular, neurological and behavioral manifestations. As opposed to acute, chronic hypomagnesemia is often underdiagnosed and underreported and as such may pose a diagnostic and therapeutic problem. CASE PRESENTATION: We describe a case of magnesium wasting in a middle-aged woman with head and neck cancer who presented with recurrent syncopal episodes complicated by a femur fracture 4 months after completing a course of carboplatin-containing chemotherapy...
February 6, 2017: Hospital Practice (Minneapolis)
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#19
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28102711/higher-expression-of-ercc1-may-be-associated-with-resistance-to-adjuvant-platinum-based-chemotherapy-in-gastric-cancer
#20
Jiayi Wan, Lin Chao, Arier C Lee, Qi Chen
Potential predictive biomarker(s) to respond to chemotherapy in gastric cancer are unclear. Excision repair cross-complementing 1 (ERCC1), a DNA repair enzyme, is associated with clinical outcomes in gastric cancer. Here, we investigated the expression of ERCC1 in gastric cancer with platinum-based chemotherapy after surgery, and the association between ERCC1 expression and clinical parameters was analyzed. Our data showed that high levels of ERCC1 expression were positively associated with resistance to platinum-based chemotherapy but not with lymph node metastasis and pathological stage...
January 19, 2017: Cancer Investigation
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