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Platinum chemotherapy resistance

Claudia Marchetti, Alessia Romito, Angela Musella, Giulia Santo, Innocenza Palaia, Giorgia Perniola, Violante Di Donato, Ludovico Muzii, Pierluigi Benedetti Panici
OBJECTIVES: In ovarian cancer (OC), approximately 70% will relapse within 12 months from diagnosis; inflammation plays an important role in cancer initiating and progression; thus, a combination of neutrophil-to-lymphocyte ratio (NLR) and fibrinogen (F-NLR) has been proposed as prognostic marker in several tumors. The aim of our study was to investigate the correlation between NLR, fibrinogen, and F-NLR and survival in OC population. METHODS: Patients with diagnosis of OC admitted to our institute between 2011 and 2016 were included...
March 14, 2018: International Journal of Gynecological Cancer
Peng Yin, Guizhen Song, Zhenhua Jiang
PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytotoxic platinum-based drug used for chemotherapy of different types of human cancers such as NPC. Nevertheless, the effects of CIS on the migration and invasion of human NPC cells and the underlying molecular mechanisms have not yet been fully scrutinized...
March 14, 2018: Cancer Chemotherapy and Pharmacology
Christoph Oing, Christoph Seidel, Carsten Bokemeyer
Most germ cell cancer patients with metastatic disease are cured by cisplatin-based combination chemotherapy. 30% of metastatic patients will develop relapse or progress despite adequate first-line treatment and will require salvage therapy, with about 10% of metastasized patients ultimately developing platinum-resistant and fatal disease. Areas covered: Based on a comprehensive literature search of MEDLINE, EMBASE and conference proceedings of ESMO, ASCO and EAU meetings, this review provides an overview on current and potential future treatment options for platinum-refractory germ cell cancer patients including cytostatics and molecularly targeted therapies...
March 8, 2018: Expert Review of Anticancer Therapy
Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Sofia Genta, Massimo Aglietta, Anna Sapino, Giorgio Valabrega
BACKGROUND: Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. OBJECTIVES: To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis...
March 5, 2018: Recent Patents on Anti-cancer Drug Discovery
Pattama Wongsirisin, Sirikan Limpakan Yamada, Supachai Yodkeeree, Wanisa Punfa, Pornngarm Limtrakul
Acquired resistance is a major reason for poor clinical outcomes in cancer chemotherapy patients. The aim of this study was to determine the sensitivity to anticancer drugs and to identify the alterations of DNA repair and drug transporter in a model of primary culture obtained from pre- and post-platinum-based anticancer treatments in nine Thai gastric cancer patients. Ex vivo sensitivity to anti-cancer drugs (cisplatin, oxaliplatin, 5-fluorouracil (5-FU) and irinotecan) was analysed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
2018: Biological & Pharmaceutical Bulletin
Belinda van Zyl, Denise Tang, Nikola A Bowden
Ovarian cancer has poor survival rate due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum resistant with subsequent relapses. Extensive research on individual biomarkers of platinum-resistance has revealed many potential targets for the development new treatments...
February 27, 2018: Endocrine-related Cancer
Maho Konishi, Asuka Imai, Masanori Fujii, Keisuke Sugimoto, Nobuyuki Katakami, Yukihiro Imai, Shingo Kamoshida
Background: Copper transporter 1 (CTR1) is a critical determinant of the uptake and cytotoxic effect of the platinum drugs carboplatin and cisplatin. Thymidylate synthase (TS) is an enzyme involved in DNA synthesis and is associated with resistance of tumor cells to 5-fluorouracil. We investigated the correlation between CTR1 and TS expression levels and treatment outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with S-1/carboplatin doublet chemotherapy. Methods: Twenty-nine patients were enrolled in this study...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Sun Min Lim, Nicholas L Syn, Byoung Chul Cho, Ross A Soo
The tyrosine kinase inhibitors (TKIs) directed at sensitizing mutations in the epidermal growth factor receptor (EGFR) gene represents a critical pillar in non-small cell lung cancer treatment. Despite the excellent disease control with initial EGFR TKI therapy, acquired resistance is ubiquitous and remains a key challenge. Investigations into the mechanisms which foster resistance to EGFR TKIs has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations...
February 20, 2018: Cancer Treatment Reviews
Katsuyuki Kiura, Fumio Imamura, Hiroshi Kagamu, Shingo Matsumoto, Toyoaki Hida, Kazuhiko Nakagawa, Miyako Satouchi, Isamu Okamoto, Mitsuhiro Takenoyama, Yasuhito Fujisaka, Takayasu Kurata, Masayuki Ito, Kota Tokushige, Ben Hatano, Makoto Nishio
Background: In the global, Phase 3, ASCEND-5 study, ceritinib improved progression-free survival (PFS) vs chemotherapy in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) who had previously progressed on crizotinib and platinum-based chemotherapy. Here, we report efficacy and safety in a subset of Japanese patients from the ASCEND-5 study. Methods: Patients with advanced ALK-rearranged NSCLC received oral ceritinib 750 mg/day or chemotherapy (intravenous pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 [investigator's choice], every 21 days)...
February 21, 2018: Japanese Journal of Clinical Oncology
Sevasti Manousakidi, Arnaud Guillaume, Caroline Pirou, Sylvina Bouleau, Bernard Mignotte, Flore Renaud, Nathalie Le Floch
Ovarian cancer remains associated with a high mortality rate and relapse is too frequently seen after chemotherapeutic treatment of granulosa cell tumors (GCTs) or epithelial ovarian cancers (EOCs). It is thus of major importance to progress in the knowledge of the molecular mechanisms underlying chemoresistance of ovarian tumors. Overexpression of Fibroblast Growth Factor 1 (FGF1) is observed in various cancers, correlates with poor survival and could be responsible for resistance to platinum-based chemotherapy of serous ovarian cancers...
February 21, 2018: Oncogenesis
Robert D Morgan, Andrew R Clamp, Jurjees Hasan, Claire Mitchell, Geoff Saunders, Nerissa Mescallado, Richard Welch, Gordon C Jayson
OBJECTIVES: Advanced-stage, platinum-resistant, ovarian cancer can be treated with dose-intense chemotherapy; one such regimen includes intravenous cisplatin and oral etoposide. To minimize the toxicity associated with weekly cisplatin, pretreatment and posttreatment hydration is required, often necessitating inpatient, overnight admission. We report a shorter, within-day regimen for delivering weekly cisplatin. METHODS: This was a retrospective study to assess the use of standard (inpatient; treatment time of 12 hours) versus modified (outpatient; treatment time of 4 hours) regimens...
March 2018: International Journal of Gynecological Cancer
Graeme Ball, Feng Xie, Jean-Eric Tarride
BACKGROUND: Ovarian cancer is a leading cause of cancer-related mortality. Although the disease is relatively rare, it carries a disproportionately large morbidity burden. OBJECTIVE: We conducted a cost-utility analysis from a Canadian public payer perspective to determine the cost effectiveness of bevacizumab, a newly available treatment option for recurrent ovarian cancer. METHODS: Using a 7-year time horizon, a three health-state cohort-based partitioned survival model was developed to assess the cost utility of bevacizumab plus chemotherapy (BEV) versus chemotherapy alone...
March 2018: PharmacoEconomics Open
Robert D Morgan, Andrew R Clamp, D Gareth R Evans, Richard J Edmondson, Gordon C Jayson
PURPOSE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have changed the management of high-grade serous ovarian cancer (HGSOC). The rationale for the development of PARPi was based on the concept of synthetic lethality, in which a cell can survive a deficiency of one gene/gene product, but may die if there is a deficiency in a combination of genes/gene products. In women with BRCA1/2 deficiency within their ovarian cancer tissue, inhibition of PARP imposes an intolerable burden of DNA damage repair deficiency and may induce cell death...
February 20, 2018: Cancer Chemotherapy and Pharmacology
Yu Zhang, Shiguo Chen, Chaoyang Wei, Gary O Rankin, Xingqian Ye, Yi Charlie Chen
Ovarian cancer is one of the leading causes of death related to the female reproductive system in western countries. Adverse side effects and resistance to platinum based chemotherapy have become the major obstacles for ovarian cancer treatment. Natural products have gained great attention in cancer treatment in recent years. Chinese bayberry leaves flavonoids (BLF) containing rich content of myricitrin (myricetin 3-O-rhamnoside) and a part of quercetrin (quercetin 3-rhamnoside) inhibited the growth of an ovarian cancer cell line A2780/CP70...
January 31, 2018: European Journal of Medicinal Chemistry
Yan Huang, Yuqi Zhou, Lingfang Xia, Jia Tang, Hao Wen, Meiqin Zhang
Platinum-based chemotherapy is the most common therapeutic regimen used to treat patients with ovarian cancer. However, the emergence of drug resistance to platinum compromises the clinical success of this treatment. Epithelial ovarian cancer is usually accompanied by an increased level of luteinizing hormone (LH). Therefore, the effect of LH on platinum resistance requires further investigation. In the current study, the effect of cisplatin and/or LH on platinum resistance was examined using the SKOV3ip1 and HeyA8 models...
March 2018: Oncology Letters
Reiko Tasaka, Takeshi Fukuda, Masahiro Shimomura, Yuta Inoue, Takuma Wada, Masaru Kawanishi, Tomoyo Yasui, Toshiyuki Sumi
The standard treatment for ovarian serous carcinoma comprises maximum debulking surgery and platinum-based chemotherapy. Despite the high response rate to chemotherapy, the majority of patients will be resistant to first-line agents and the prognosis for these patients is particularly poor. At present there are no reliable methods to determine or predict platinum resistance. T-box 2 (TBX2) is widely expressed in cancer cells and is involved in embryonic development and cell cycle regulation. TBX2 enables cells to bypass senescence through its ability to repress the cell cycle regulators p21 and p14ARF; silencing TBX2 induces senescence...
March 2018: Oncology Letters
San-Duk Yang, So Hee Ahn, Jong-Il Kim
Ovarian cancer (OC) is the second leading cause of mortality from gynecological malignancies and has the highest mortality rate worldwide. As it is commonly asymptomatic during the early stages of the disease, >70% of patients with OC are diagnosed at advanced stages with metastasis. Despite treatment methods, including optimal debulking surgery and chemotherapy with the platinum-based drug cisplatin, OC recurrence is often inevitable, with an overall 5-year survival rate of 45%, mostly due to the steady development of cisplatin resistance...
February 2018: Oncology Letters
Pauraic Mc Carron, Aisling Crowley, Denis O'Shea, Malachy McCann, Orla Howe, Mary Hunt, Michael Devereux
The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor's overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established...
February 9, 2018: Current Medicinal Chemistry
Kathleen N Moore, Ignace Vergote, Ana Oaknin, Nicoletta Colombo, Susana Banerjee, Amit Oza, Patricia Pautier, Karim Malek, Michael J Birrer
Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-α to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease. Here we describe the rationale and design of FORWARD I (NCT02631876), the first randomized, multicenter Phase III study to compare the safety and efficacy of mirvetuximab soravtansine versus investigator's choice of chemotherapy in women with folate receptor-α-positive, platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer...
February 9, 2018: Future Oncology
I Buß, A Hamacher, N Sarin, M U Kassack, G V Kalayda
Oxaliplatin is a routinely used drug in the treatment of colorectal cancer. However, development of resistance is a major hurdle of the chemotherapy success. Defects in cellular accumulation represent a frequently reported feature of cells with acquired resistance to platinum drugs. Nevertheless, the mechanisms of oxaliplatin uptake and their role in oxaliplatin resistance remain poorly elucidated. The aim of this study was to investigate the relevance of copper transporter 1 (CTR1) and organic cation transporters 1-3 (OCT1-3) for oxaliplatin uptake and resistance to the drug in sensitive and oxaliplatin-resistant ileocecal colorectal adenocarcinoma cells...
February 8, 2018: Metallomics: Integrated Biometal Science
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