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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#1
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n=80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28079002/neurotoxicity-associated-with-platinum-based-anti-cancer-agents-what-are-the-implications-of-copper-transporters
#2
Vanesa Stojanovska, Rachel McQuade, Emma Rybalka, Kulmira Nurgali
Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of interstrand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28074905/mir-488-inhibits-proliferation-and-cisplatin-sensibility-in-non-small-cell-lung-cancer-nsclc-cells-by-activating-the-eif3a-mediated-ner-signaling-pathway
#3
Chao Fang, Yi-Xin Chen, Na-Yiyuan Wu, Ji-Ye Yin, Xiang-Ping Li, Hsuan-Shun Huang, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3'UTR of eIF3a...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032148/the-relationship-between-platinum-drug-resistance-and-epithelial-mesenchymal-transition
#4
REVIEW
Anamaria Brozovic
One of the most commonly used chemotherapeutics, platinum drugs are used to treat a wide range of cancer types. Although many cancers initially respond well to those drugs, drug resistance occurs frequently and different molecular mechanisms have been associated with it. However, predictive biomarkers of cellular response in specific tumour types still do not exist. Epithelial-mesenchymal transition (EMT) is a malignant cancer phenotype characterized by aggressive invasion and metastasis, and resistance to apoptosis...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28031529/the-prognostic-value-of-ki67-in-ovarian-high-grade-serous-carcinoma-an-11-year-cohort-study-of-chinese-patients
#5
Ming Chen, Shuzhong Yao, Qinghua Cao, Meng Xia, Junxiu Liu, Mian He
OBJECTIVE: This study sought to assess the prognostic role of Ki67 in primary ovarian high-grade serous carcinoma (HGSC) and to determine whether Ki67 expression can predict responsiveness to platinum and paclitaxel chemotherapy. RESULTS: A total of 318 women were included in the analysis and the median follow-up time was 48 months (range, 3-150 months). Ki67 proliferation indices ranged from 3% to 95% with a median of 40%. Using 40% as the cut-off value for the Ki67 index, we classified 141 patients as having low Ki67 expression and 177 patients as having high Ki67 expression...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027849/chemotherapy-for-epithelial-ovarian-fallopian-tube-and-primary-peritoneal-cancer
#6
REVIEW
Kate Webber, Michael Friedlander
Chemotherapy plays a key role in the management of women with epithelial ovarian, fallopian tube and primary peritoneal cancer (EOC). Platinum- and taxane-based regimens are the standard of care for adjuvant treatment in early-stage EOC and first-line therapy for advanced stage disease. Efforts to define the optimal scheduling, timing and route of administration are ongoing. The majority of women with EOC will develop recurrent disease, and treatment options for these women are depend on the time that has elapsed from first-line therapy...
November 23, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/27989629/-50th-anniversary-of-cisplatin
#7
REVIEW
Chloé Rancoule, Jean-Baptiste Guy, Alexis Vallard, Majed Ben Mrad, Amel Rehailia, Nicolas Magné
We have just celebrated the 50th anniversary of cisplatin cytotoxic potential discovery. It is time to take stock… and it seems mainly positive. This drug, that revolutionized the treatment of many cancer types, continues to be the most widely prescribed chemotherapy. Despite significant toxicities, resistance mechanisms associated with treatment failures, and unresolved questions about its mechanism of action, the use of this cytotoxic agent remains unwavering. The interest concerning this "old" invincible drug has not yet abated...
December 15, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27988838/polymorphisms-of-genes-encoding-multidrug-resistance-proteins-as-a-predictive-factor-for-second-line-docetaxel-therapy-in-advanced-non-small-cell-lung-cancer
#8
Michał Szczyrek, Radosław Mlak, Paweł Krawczyk, Kamila Wojas-Krawczyk, Tomasz Powrózek, Aneta Szudy-Szczyrek, Agnieszka Zwolak, Jadwiga Daniluk, Janusz Milanowski
Multidrug resistance (MDR) remains a substantial problem in chemotherapy. The purpose of the study was to investigate potential factors, including MDR genes polymorphisms, that could be used in qualification for second-line docetaxel therapy in non-small cell lung cancer (NSCLC) patients after failure of platinum based chemotherapy. Study group comprised of 58 Caucasian subjects. Evaluation of Single Nucleotide Polymorphisms (SNPs) of ABCC2/MRP2 and ABCB1/MDR1 genes was performed using the High Resolution Melting (HRM) technique...
December 17, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27980217/the-association-between-copper-transporters-and-the-prognosis-of-cancer-patients-undergoing-chemotherapy-a-meta-analysis-of-literatures-and-datasets
#9
REVIEW
Si Sun, Jing Cai, Qiang Yang, Simei Zhao, Zehua Wang
Copper transporter 1 (CTR1), copper transporter 2 (CTR2), copper-transporting p-type adenosine triphosphatase 1 and 2 (ATP7A and ATP7B) are key mediators of cellular cisplatin, carboplatin and oxaliplatin accumulation. In this meta-analysis, we aimed to evaluate the relation of CTR1, CTR2, ATP7A and ATP7B to overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and treatment response (TR) of cancer patients who received chemotherapy based on published literatures, the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets...
December 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27941566/folate-receptor-alpha-expression-in-platinum-resistant-refractory-ovarian-carcinomas-and-primary-endocervical-adenocarcinomas
#10
Lisa A Rubinsak, Cynthia Cohen, Namita Khanna, Ira R Horowitz, Krisztina Z Hanley
INTRODUCTION: Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used...
December 9, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27936622/dna-adducts-from-anticancer-drugs-as-candidate-predictive-markers-for-precision-medicine
#11
Alessia Stornetta, Maike Zimmermann, George D Cimino, Paul T Henderson, Shana J Sturla
Biomarker-driven drug selection plays a central role in cancer drug discovery and development, and in diagnostic strategies to improve the use of traditional chemotherapeutic drugs. DNA-modifying anticancer drugs are still used as first line medication, but drawbacks such as resistance and side effects remain an issue. Monitoring the formation and level of DNA modifications induced by anticancer drugs is a potential strategy for stratifying patients and predicting drug efficacy. In this perspective, preclinical and clinical data concerning the relationship between drug-induced DNA adducts and biological response for platinum drugs and combination therapies, nitrogen mustards and half-mustards, hypoxia-activated drugs, reductase-activated drugs, and minor groove binding agents are presented and discussed...
January 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27935223/response-to-and-toxicity-of-gemcitabine-for-recurrent-ovarian-cancer-according-to-number-of-previous-chemotherapy-regimens
#12
Yuji Takei, Yoshifumi Takahashi, Shizuo Machida, Akiyo Taneichi, Suzuyo Takahashi, Tomomi Nagashima, Hiroyuki Morisawa, Yasushi Saga, Shigeki Matsubara, Hiroyuki Fujiwara
AIM: Gemcitabine is used not only as a second-line, but also as a third-line or higher regimen for taxane/platinum-resistant recurrent ovarian cancer. The purpose of this study was to clarify the response to and toxicity of gemcitabine for recurrent ovarian cancer according to the number of previous chemotherapy regimens. METHODS: The subjects were patients with taxane/platinum-resistant recurrent ovarian cancer on gemcitabine treatment at the present hospital between June 2007 and September 2013...
December 9, 2016: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#13
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27919980/intraperitoneal-chemotherapy-in-patients-pretreated-for-ovarian-cancer-matched-with-patients-treated-with-parenteral-chemotherapy
#14
Maria Ornella Nicoletto, Alessandra Casarin, Alessandra Baldoni, Eliana Rulli, Giulia Tasca, Zora Baretta, Grazia Artioli, Giuseppe Lombardi, Alessandro Cappetta, Irene Floriani, Giovanni Randon, Sara Valpione, Piero Litta, Pierfranco Conte, Simone Mocellin, Camillo Aliberti
BACKGROUND: Our aim was to analyze the impact of intraperitoneal chemotherapy (IPC), administered with direct peritoneal puncture, on the survival of patients with pretreated ovarian cancer in a real-life setting. PATIENTS AND METHODS: This was a retrospective study comparing patients with advanced ovarian cancer treated with IPC (N=33) and patients treated with standard intravenous (i.v.) chemotherapy matching cases for known prognostic factors (age, platinum sensitivity, histological subgroup and grade)...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27918136/development-of-cell-permeable-non-helical-constrained-peptides-to-target-a-key-protein-protein-interaction-in-ovarian-cancer
#15
Mareike M Wiedmann, Yaw Sing Tan, Yuteng Wu, Shintaro Aibara, Wenshu Xu, Hannah F Sore, Chandra S Verma, Laura Itzhaki, Murray Stewart, James D Brenton, David R Spring
There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines. To inhibit the protein function, cell-permeable, non-helical constrained proteomimetics to target the HNF1β-importin α protein-protein interaction were designed, guided by X-ray crystallographic data and molecular dynamics simulations...
January 9, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27914067/5q-syndrome-like-features-as-the-first-manifestation-of-myelodysplastic-syndrome-in-a-patient-with-an-unbalanced-whole-arm-translocation-der-5-19-p10-q10
#16
Hiroshi Ureshino, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before...
December 2, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27903924/randomized-phase-ii-study-of-cabazitaxel-versus-methotrexate-in-patients-with-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-previously-treated-with-platinum-based-therapy
#17
Jean-Pascal Machiels, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stéphanie Henry, Lionel D'Hondt, Christophe Lonchay, Stéphane Holbrechts, Petra Boegner, Dany Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Aline Gillain, Joelle Schoonjans, Sylvie Rottey
LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%)...
December 2016: Oncologist
https://www.readbyqxmd.com/read/27903751/microdose-induced-drug-dna-adducts-as-biomarkers-of-chemotherapy-resistance-in-humans-and-mice
#18
Maike Zimmermann, Si-Si Wang, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Ted Ognibene, Hongyuan Yang, Susan Airhart, Kenneth W Turteltaub, George D Cimino, Clifford G Tepper, Alexandra Drakaki, Karim Chamie, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#19
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27895753/drug-resistance-analysis-of-gefitinib-targeted-therapy-in-non-small-cell-lung-cancer
#20
Shuliang Liu, Hongji Yang, Xingping Ge, Lingfei Su, Aifeng Zhang, Liang Liang
The aim of the study was to examine the drug resistance analysis of gefitinib-targeted therapy in non-small cell lung cancer (NSCLC). In total, 156 NSCLC patients without surgical treatment were selected, including 117 cases of adenocarcinoma (75%), to receive single gefitinib 0.25 g/day or combined with platinum chemotherapy. Computed tomography was used to evaluate tumor growth for the response and non-response groups. The chemotherapy regimen was changed or combined with radiotherapy in the non-response group...
November 2016: Oncology Letters
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