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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28746345/cisplatin-resistance-in-non-small-cell-lung-cancer-cells-is-associated-with-an-abrogation-of-cisplatin-induced-g2-m-cell-cycle-arrest
#1
Navin Sarin, Florian Engel, Ganna V Kalayda, Mareike Mannewitz, Jindrich Cinatl, Florian Rothweiler, Martin Michaelis, Hisham Saafan, Christoph A Ritter, Ulrich Jaehde, Roland Frötschl
The efficacy of cisplatin-based chemotherapy in cancer is limited by the occurrence of innate and acquired drug resistance. In order to better understand the mechanisms underlying acquired cisplatin resistance, we have compared the adenocarcinoma-derived non-small cell lung cancer (NSCLC) cell line A549 and its cisplatin-resistant sub-line A549rCDDP2000 with regard to cisplatin resistance mechanisms including cellular platinum accumulation, DNA-adduct formation, cell cycle alterations, apoptosis induction and activation of key players of DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28738967/-recent-advances-in-association-of-estrogen-and-non-small-cell-lung-cancer
#2
Xiaosheng Ding, Chuanhao Tang, Zhijie Wang, Jun Liang
Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC), is one of the most prevalent cancers and the most leading cause of cancer mortality. Despite recent improvements in its treatment, the prognosis remains dismal. Previous studies have clearly proved that estrogen and estrogen receptors (ER) are involve in the pathogenesis and development of lung cancer. More and more evidences showed antiestrogen therapy may reverse the drug-resistance of platinum based chemotherapy in NSCLC patients and can enhance curative effect of epidermal growth factor receptor tyrosine kinase inhibitor...
July 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28737129/association-between-polymorphisms-in-ctr1-ctr2-atp7a-and-atp7b-and-platinum-resistance-in-epithelial-ovarian-cancer
#3
Tailin Li, Jingbo Peng, Feiyue Zeng, Keqiang Zhang, Jinyang Liu, Xi Li, Qianying Ouyang, Guo Wang, Liansheng Wang, Zhaoqian Liu, Yingzi Liu
The copper transporters CTR1, CTR2, ATP7A, and ATP7B regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in CTR1, CTR2, ATP7A, and ATP7B on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28730758/platinum-derivatives-a-multidisciplinary-approach
#4
Sinziana Gheorghe-Cetean, Calin Cainap, Luminita Oprean, Adriana Hangan, Piroska Virag, Eva Fischer-Fodor, Alexandra Gherman, Simona Cainap, Anne-Marie Constantin, Istvan Laszlo, Catalin Vlad, Radu Oprean
Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28714373/targeting-mir-21-decreases-expression-of-multi-drug-resistant-genes-and-promotes-chemosensitivity-of-renal-carcinoma
#5
Kelly Gaudelot, Jean-Baptiste Gibier, Nicolas Pottier, Brigitte Hémon, Isabelle Van Seuningen, François Glowacki, Xavier Leroy, Christelle Cauffiez, Viviane Gnemmi, Sébastien Aubert, Michaël Perrais
Renal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In this study, we focused our attention on miR-21, a well described oncomiR commonly upregulated in cancer. Using a cohort of 99 primary renal cell carcinoma samples, we showed that miR-21 expression in cancer tissues was higher than in adjacent non-tumor tissues whereas no significant difference was observed with stages, grades, and metastatic outcome...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28712484/relevance-of-dna-damage-repair-in-the-management-of-prostate-cancer
#6
Patricia Banks, Wen Xu, Declan Murphy, Paul James, Shahneen Sandhu
Recent insights into the genomic aberrations that underlie and drive prostate cancer have redoubled efforts to molecularly stratify treatments based on predictive markers. Approximately 23% of patients with metastatic castration-resistant prostate cancer exhibit somatic or germline aberrations in genes implicated in DNA repair, such as BRCA2, BRCA1, ATM, CHEK2, and PALB2, as well as mismatch repair genes. At least 10% of men with advanced disease have germline mutations in DNA-repair genes (DRG). The enrichment of DRG defects in metastatic disease compared with localized, primary tumors suggests a possible role in carcinogenesis, disease progression, and potentially accounts for a more aggressive phenotype...
June 27, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28712280/radiation-for-persistent-or-recurrent-epithelial-ovarian-cancer-a-need-for-reassessment
#7
Noorie Choi, Ji Hyun Chang, Suzy Kim, Hak Jae Kim
PURPOSE: The role of radiotherapy (RT) was largely deserted after the introduction of platinum-based chemotherapy, but still survival rates are disappointingly low. This study focuses on assessing the clinical efficacy of RT in relation to chemotherapy resistance. MATERIALS AND METHODS: From October 2002 to January 2015, 44 patients were diagnosed with epithelial ovarian cancer (EOC) and treated with palliative RT for persistent or recurrent EOC. All patients received initial treatment with optimal debulking surgery and adjuvant platinum-based chemotherapy...
June 2017: Radiation Oncology Journal
https://www.readbyqxmd.com/read/28710915/potent-therapeutic-activity-against-peritoneal-dissemination-and-malignant-ascites-by-the-novel-anti-folate-receptor-alpha-antibody-khk2805
#8
Munetoshi Ando, Keiko Nagata, Kaito Nihira, Yui Suzuki, Yutaka Kanda, Maiko Adachi, Tsuguo Kubota, Naoya Kameyama, Mariko Nakano, Hiroshi Ando, Kazuya Yamano, Toshihiko Ishii, Ryuichiro Nakai, Kazuyasu Nakamura
Many ovarian cancer patients often show peritoneal metastasis with malignant ascites. However, unmet medical needs remain regarding controlling these symptoms after tumors become resistant to chemotherapies. We developed KHK2805, a novel anti-folate receptor α (FOLR1) humanized antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The primary aim of the present study was to evaluate whether the anti-tumor activity of KHK2805 was sufficient for therapeutic application against peritoneal dissemination and malignant ascites of platinum-resistant ovarian cancer in preclinical models...
July 11, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28696006/genetic-variation-in-the-dna-repair-pathway-as-a-potential-determinant-of-response-to-platinum-based-chemotherapy-in-breast-cancer
#9
REVIEW
Farimah Beheshti, Seyed Mahdi Hassanian, Majid Khazaei, Mahmoud Hosseini, Soodabeh ShahidSales, Malihe Hasanzadeh, Mina Maftouh, Gordon A Ferns, Amir Avan
Platinum-based chemotherapy is often used as a first-line treatment for patient with breast cancer. Platinum agents bind to DNA, forming adducts that contain intra and inter-strand crosslinks. It is possible that genetic variations of the DNA repair pathways may affect the activity, or efficacy of platinum, and hence resistance to platinum chemotherapy may be related to these genetic variants. We have summarized the known variants in the DNA repair pathway that have been reported to predict the response to platinum-based therapy in breast cancer...
July 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#10
Daolu Yuwen, Shanwei Mi, Yuzhu Ma, Wenjie Guo, Qiang Xu, Yan Shen, Yongqian Shu
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28685693/multi-targeted-anticancer-agents
#11
Wei Zheng, Yao Zhao, Qun Luo, Yang Zhang, Kui Wu, Fuyi Wang
There is great demand for the development of novel anticancer drugs, due to the increasing morbidity and high mortality of cancer. To date, chemotherapy still plays a central role in the clinical treatment of cancer, but this role is being reduced by targeted therapies. Since cancer is a complicated and multiple genes involved disease, drugs that act at multiple targets can enhance efficacy and lower drug resistance, and are thought to be the future of novel anticancer drug development. In this paper, we discuss the recent development of "single molecule, multi-target" anticancer agents that combine two or more pharmacophores in a single molecule, including organic multi-targeted anticancer agents and metal based complexes such as platinum, ruthenium, iridium and rhodium complexes...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28683123/reverse-epithelial-mesenchymal-transition-contributes-to-the-regain-of-drug-sensitivity-in-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer-cells
#12
An-Fu Lee, Man-Chin Chen, Chao-Ju Chen, Chih-Jen Yang, Ming-Shyang Huang, Yu-Peng Liu
Tyrosine kinase inhibitors (TKIs) are currently the first-line treatment for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. These patients receive platinum-based chemotherapy as the second-line treatment after they develop resistance to TKIs. Many patients regain sensitivity to the TKIs used in the first-line treatment after the failure of chemotherapy. However, the molecular mechanism for the regain of TKI sensitivity is largely unknown. In this study, we established gefitinib-resistant PC9 and HCC827 cell lines, which did not harbor the EGFR T790M mutation and MET amplification but exhibited the epithelial-mesenchymal transition (EMT) phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28676222/optimal-management-of-egfr-mutant-non-small-cell-lung-cancer-with-disease-progression-on-first-line-tyrosine-kinase-inhibitor-therapy
#13
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, and the second-generation EGFR-TKI, afatinib, have all been approved as standard first-line treatments for advanced EGFR-mutant non-small cell lung cancer (NSCLC) based on superior progression-free survival results compared to platinum doublet chemotherapy regimens. Acquired resistance to an EGFR-TKI inevitably develops after a period of effective drug treatment. After tumor progression, many combination therapy regimens that include an EGFR-TKI, or EGFR-TKI monotherapy, have been tested in prospective trials with the aim of extending survival...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28666422/the-role-of-hormonal-therapy-in-patients-with-relapsed-high-grade-ovarian-carcinoma-a-retrospective-series-of-tamoxifen-and-letrozole
#14
Angela George, Jennifer McLachlan, Nina Tunariu, Chiara Della Pepa, Cristina Migali, Martin Gore, Stan Kaye, Susana Banerjee
BACKGROUND: Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors. Our aim was to evaluate the efficacy of tamoxifen (T) and letrozole (L) in HGOC in clinical practice and investigate factors influencing clinical outcome. METHODS: A retrospective review of patients with relapsed HGOC treated with either tamoxifen or letrozole at the Royal Marsden Hospital between 2007 and 2012 was performed...
June 30, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28662677/a-phase-i-ii-trial-of-fixed-dose-stereotactic-body-radiotherapy-with-sequential-or-concurrent-pembrolizumab-in-metastatic-urothelial-carcinoma-evaluation-of-safety-and-clinical-and-immunologic-response
#15
Nora Sundahl, Katrien De Wolf, Sylvie Rottey, Karel Decaestecker, Daan De Maeseneer, Annabel Meireson, Els Goetghebeur, Valérie Fonteyne, Sofie Verbeke, Pieter De Visschere, Dries Reynders, Mireille Van Gele, Lieve Brochez, Piet Ost
BACKGROUND: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment...
June 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28659181/prognostic-and-predictive-factors-in-patients-with-metastatic-or-recurrent-cervical-cancer-treated-with-platinum-based-chemotherapy
#16
Sofia Karageorgopoulou, Ioannis D Kostakis, Maria Gazouli, Sonia Markaki, Marios Papadimitriou, Evangelos Bournakis, Meletios-Athanassios Dimopoulos, Christos A Papadimitriou
BACKGROUND: Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. METHODS: Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers...
June 28, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28656383/a-phase-ii-study-of-irinotecan-and-pegylated-liposomal-doxorubicin-in-platinum-resistant-recurrent-ovarian-cancer-tohoku-gynecologic-cancer-unit-104-study
#17
Tadahiro Shoji, Eriko Takatori, Hideo Omi, Masahiro Kagabu, Tatsuya Honda, Masayuki Futagami, Yoshihito Yokoyama, Michiko Kaiho, Hideki Tokunaga, Takeo Otsuki, Tadao Takano, Nobuo Yaegashi, Takanobu Kojimahara, Tsuyoshi Ohta, Satoru Nagase, Shu Soeda, Takafumi Watanebe, Hiroshi Nishiyama, Toru Sugiyama
PURPOSE: We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial. METHODS: PLD was administered intravenously at a dose of 30 mg/m(2) on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m(2) on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression...
June 27, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#18
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28645491/systematic-review-of-immune-checkpoint-inhibition-in-urological-cancers
#19
REVIEW
Maud Rijnders, Ronald de Wit, Joost L Boormans, Martijn P J Lolkema, Astrid A M van der Veldt
CONTEXT: In patients with advanced and metastatic urological cancers, clinical outcome may be improved by immune checkpoint inhibitors (ICIs). OBJECTIVE: To systematically review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. EVIDENCE ACQUISITION: Relevant databases, including Medline, Embase, and the Cochrane Library, were searched up to March 16, 2017...
June 20, 2017: European Urology
https://www.readbyqxmd.com/read/28641578/methylome-analysis-of-extreme-chemoresponsive-patients-identifies-novel-markers-of-platinum-sensitivity-in-high-grade-serous-ovarian-cancer
#20
Tushar Tomar, Nicolette G Alkema, Leroy Schreuder, Gert Jan Meersma, Tim de Meyer, Wim van Criekinge, Harry G Klip, Heidi Fiegl, Els van Nieuwenhuysen, Ignace Vergote, Martin Widschwendter, Ed Schuuring, Ate G J van der Zee, Steven de Jong, G Bea A Wisman
BACKGROUND: Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients. The objective of this study was to identify and validate novel epigenetic markers of chemoresponse using genome-wide analysis of DNA methylation in extreme chemoresponsive HGSOC patients...
June 23, 2017: BMC Medicine
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