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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28932630/the-safety-efficacy-and-treatment-outcomes-of-a-combination-of-low-dose-decitabine-treatment-in-patients-with-recurrent-ovarian-cancer
#1
Yan Zhang, Qian Mei, Yang Liu, Xiang Li, Malcolm V Brock, Meixia Chen, Liang Dong, Lu Shi, Yao Wang, Mingzhou Guo, Jing Nie, Weidong Han
Purpose: DNA demethylating agents have shown clinical effectiveness in hematological and solid tumors. This trial tested the safety, efficacy, and treatment outcomes of decitabine-based chemotherapy or combined with immunotherapy in recurrent ovarian cancer patients. Patients and methods: Fifty-five patients with recurrent ovarian cancer were enrolled and 52 were assessable for clinical response and survival. Patients either received 5-d decitabine treatment, followed by reduced-dose of paclitaxel/carboplatin administration (DTC cohort), or the aforementioned regimen combined with cytokine-induced killer cells therapy (DTC+CIK cohort)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28927094/genomic-markers-of-ovarian-adenocarcinoma-and-its-relevancy-to-the-effectiveness-of-chemotherapy
#2
Monika Englert-Golon, Bartosz Burchardt, Bartlomiej Budny, Szymon Dębicki, Blanka Majchrzycka, Elzbieta Wrotkowska, Piotr Jasiński, Katarzyna Ziemnicka, Radosław Słopień, Marek Ruchała, Stefan Sajdak
Ovarian cancer is the eighth most common cancer and the seventh highest cause of cancer-associated mortality in women worldwide. It is the second highest cause of mortality among female reproductive malignancies. The current standard first-line treatment for advanced ovarian cancer includes a combination of surgical debulking and standard systemic platinum-based chemotherapy with carboplatin and paclitaxel. Although a deeper understanding of this disease has been attained, relapse occurs in 70% of patients 18 months subsequent to the first-line treatment...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926265/tobacco-mosaic-virus-delivered-cisplatin-restores-efficacy-in-platinum-resistant-ovarian-cancer-cells
#3
Christina E Franke, Anna E Czapar, Ravi B Patel, Nicole F Steinmetz
Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells...
September 19, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28922711/current-updates-on-micrornas-as-regulators-of-chemoresistance
#4
REVIEW
Metin Çalışkan, Hale Güler, Vildan Bozok Çetintaş
Resistance to chemotherapeutics including platinum agents, nucleoside analogues, topoisomerase and microtubule inhibitors is the most important problem in the treatment of many cancer. Several resistance mechanisms has been described for each group and researchers have been trying to develop new approaches to overcome chemoresistance. miRNAs are the regulators of gene transcription at the post-transcriptional level. Dysregulated miRNAs have been reported in cancer tumorigenesis, diagnosis and prognosis and they are promising new therapeutic approaches to improve diagnosis and predictions of outcomes and response to chemotherapy...
September 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28918032/microrna-31-regulates-chemosensitivity-in-malignant-pleural-mesothelioma
#5
Hannah L Moody, Michael J Lind, Stephen G Maher
Malignant pleural mesothelioma (MPM) is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31) is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917596/response-rate-to-chemotherapy-after-immune-checkpoint-inhibition-in-metastatic-urothelial-cancer
#6
Bernadett Szabados, Nick van Dijk, Yen Zhi Tang, Michiel van der Heijden, Akhila Wimalasingham, Alfonso Gomez de Liano, Simon Chowdhury, Simon Hughes, Sarah Rudman, Mark Linch, Thomas Powles
Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described (n=28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1...
September 13, 2017: European Urology
https://www.readbyqxmd.com/read/28904804/bringing-new-medicines-to-women-with-epithelial-ovarian-cancer-what-is-the-unmet-medical-need
#7
REVIEW
Thomas J Herzog, Bradley J Monk
BACKGROUND: Therapy for advanced epithelial ovarian cancer (OC) includes first line platinum/taxane-containing chemotherapy and re-treatment with platinum-containing regimens for disease recurrence in patients likely to respond again. Single-agent, non-platinum, cytotoxic agents are commonly used to treat patients resistant to platinum retreatment, but these agents are associated with dose-limiting toxicities and response rates below 20%. MAIN BODY: Recent advances have led to novel targeted treatments for recurrent OC that offer opportunities to improve response rates and prolong progression-free intervals...
2017: Gynecologic Oncology Research and Practice
https://www.readbyqxmd.com/read/28894827/the-genetic-landscape-of-programmed-death-ligand-1-pd-l1-alterations-in-head-and-neck-cancer
#8
Thomas E Heineman, Adam Widman, Edward C Kuan, Maie St John
OBJECTIVES: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets...
June 2017: Laryngoscope Investigative Otolaryngology
https://www.readbyqxmd.com/read/28882436/antitumor-activity-and-safety-of-the-parp-inhibitor-rucaparib-in-patients-with-high-grade-ovarian-carcinoma-and-a-germline-or-somatic-brca1-or-brca2-mutation-integrated-analysis-of-data-from-study-10-and-ariel2
#9
Amit M Oza, Anna V Tinker, Ana Oaknin, Ronnie Shapira-Frommer, Iain A McNeish, Elizabeth M Swisher, Isabelle Ray-Coquard, Katherine Bell-McGuinn, Robert L Coleman, David M O'Malley, Alexandra Leary, Lee-May Chen, Diane Provencher, Ling Ma, James D Brenton, Gottfried E Konecny, Cesar M Castro, Heidi Giordano, Lara Maloney, Sandra Goble, Kevin K Lin, James Sun, Mitch Raponi, Lindsey Rolfe, Rebecca S Kristeleit
OBJECTIVE: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). METHODS: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy...
September 4, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28860885/osimertinib-in-the-treatment-of-non-small-cell-lung-cancer-design-development-and-place-in-therapy
#10
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Giuseppe Altavilla, Rafael Rosell
The discovery of epidermal growth factor receptor (EGFR) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior efficacy and better toxicity compared with first-line platinum-based chemotherapy and currently represent the standard of care for EGFR-mutated advanced NSCLC patients...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28860445/-efficacy-of-gc-therapy-for-the-patient-of-itnbc-with-resistance-to-tac-therapy
#11
Mai Yamada, Makoto Kubo, Masaya Kai, Hidetaka Yamamoto, Masafumi Nakamura
We report a case of TNBC treated effectively with a platinum-based regimen after developing resistance to anthracycline and taxane-based neoadjuvant chemotherapy(NAC). A 59-year-old woman with a right breast mass and high fever visited our clinic and was diagnosed as having inflammatory triple negative breast cancer(iTNBC). She was treated with NAC of docetaxel, doxorubicin, and cyclophosphamide(TAC)using pegfilgrastim. After 5 courses of TAC, the therapy failed and the disease progressed. Thus, a combination regimen of gemcitabine and carboplatin(GC)was administered...
August 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28851888/the-prognostic-97-chemoresponse-gene-signature-in-ovarian-cancer
#12
Abel Matondo, Yong Hwa Jo, Muhammad Shahid, Tae Gyu Choi, Minh Nam Nguyen, Ngoc Ngo Yen Nguyen, Salima Akter, Insug Kang, Joohun Ha, Chi Hoon Maeng, Si-Young Kim, Ju-Seog Lee, Jayoung Kim, Sung Soo Kim
Patient diagnosis and care would be significantly improved by understanding the mechanisms underlying platinum and taxane resistance in ovarian cancer. Here, we aim to establish a gene signature that can identify molecular pathways/transcription factors involved in ovarian cancer progression, poor clinical outcome, and chemotherapy resistance. To validate the robustness of the gene signature, a meta-analysis approach was applied to 1,020 patients from 7 datasets. A 97-gene signature was identified as an independent predictor of patient survival in association with other clinicopathological factors in univariate [hazard ratio (HR): 3...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839145/dact1-overexpression-in-type-i-ovarian-cancer-inhibits-malignant-expansion-and-cis-platinum-resistance-by-modulating-canonical-wnt-signalling-and-autophagy
#13
Ruo-Nan Li, Bin Liu, Xue-Mei Li, Liang-Si Hou, Xiao-Ling Mu, Hui Wang, Hua Linghu
Type I epithelial ovarian cancer (EOC) is primarily resistant to platinum-based chemotherapies and needs novel therapeutics. Given the aberrant Wnt activation in type I EOC and the involvement of Dapper1 Antagonist of Catenin-1 (DACT1) in Wnt signalling, the role of DACT1 in tumourigenesis of type I EOC was evaluated. Firstly, all tested EOC cell lines and primary EOC tissues, especially type I EOC, were observed to have significantly lower DACT1 expression than normal controls. Next, 3AO cells, which arise from a patient with primary mucinous EOC and express low endogenous levels of DACT1, were transfected with a lentivirus carrying full-length DACT1 (3AO-DACT1), grew slower and formed smaller tumours in nude mice compared to 3AO-NC...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28834763/overcoming-resistance-to-cisplatin-by-inhibition-of-glutathione-s-transferases-gsts-with-ethacraplatin-micelles-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
Shuyi Li, Chan Li, Shubin Jin, Juan Liu, Xiangdong Xue, Ahmed Shaker Eltahan, Jiadong Sun, Jingjie Tan, Jinchen Dong, Xing-Jie Liang
Platinum-based DNA-adducting agents are used extensively in the clinic for cancer chemotherapy. However, the anti-tumor efficacy of these drugs is severely limited by cisplatin resistance, and this can lead to the failure of chemotherapy. One of cisplatin resistance mechanisms is associated with overexpression of glutathione S-transferases (GSTs), which would accelerate the deactivation of cisplatin and decrease its antitumor efficiency. Nanoscale micelles encapsulating ethacraplatin, a conjugate of cisplatin and ethacrynic acid (an effective GSTs inhibitor), can enhance the accumulation of active cisplatin in cancer cells by inhibiting the activity of GSTs and circumventing deactivation of cisplatin...
August 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28831036/brca-locus-specific-loss-of-heterozygosity-in-germline-brca1-and-brca2-carriers
#15
Kara N Maxwell, Bradley Wubbenhorst, Brandon M Wenz, Daniel De Sloover, John Pluta, Lyndsey Emery, Amanda Barrett, Adam A Kraya, Ioannis N Anastopoulos, Shun Yu, Yuchao Jiang, Hao Chen, Nancy R Zhang, Nicole Hackman, Kurt D'Andrea, Robert Daber, Jennifer J D Morrissette, Nandita Mitra, Michael Feldman, Susan M Domchek, Katherine L Nathanson
Complete loss of BRCA1 or BRCA2 function is associated with sensitivity to DNA damaging agents. However, not all BRCA1 and BRCA2 germline mutation-associated tumors respond. Herein we report analyses of 160 BRCA1 and BRCA2 germline mutation-associated breast and ovarian tumors. Retention of the normal BRCA1 or BRCA2 allele (absence of locus-specific loss of heterozygosity (LOH)) is observed in 7% of BRCA1 ovarian, 16% of BRCA2 ovarian, 10% of BRCA1 breast, and 46% of BRCA2 breast tumors. These tumors have equivalent homologous recombination deficiency scores to sporadic tumors, significantly lower than scores in tumors with locus-specific LOH (ovarian, P = 0...
August 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819699/cudc-907-a-dual-hdac-and-pi3k-inhibitor-reverses-platinum-drug-resistance
#16
Kenneth K W To, Li-Wu Fu
Platinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test for the circumvention of resistance by CUDC-907...
August 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819441/vsv-based-virotherapy-in-ovarian-cancer-the-past-the-present-and-%C3%A2-future
#17
REVIEW
Beata Urszula Orzechowska, Marcin Jędryka, Katarzyna Zwolińska, Rafał Matkowski
The standard approach to treating patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery remains taxane and platinum-based chemotherapy. Despite treatment with this strategy, the vast majority of patients relapse and develop drug-resistant metastatic disease that may be driven by cancer stem cells (CSCs) or cancer initiating cells (CICs). Oncolytic viruses circumvent typical drug-resistance mechanisms, therefore they may provide a safe and effective alternative treatment for chemotherapy-resistant CSCs/CICs...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#18
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28800871/malignant-pleural-mesothelioma-state-of-the-art-and-advanced-cell-therapy
#19
Giorgio Facchetti, Francesco Petrella, Lorenzo Spaggiari, Isabella Rimoldi
Malignant Pleural Mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy, with a response rate of 20% of patients and for this reason an efficient treatment is still a challenge. Platinum-based chemotherapy in association with a third-generation antifolate is the front-line standard of care whereas any second-line treatment was approved for MPM thus making it a pathology that evokes the need for new therapeutic agents. Different platinum-drugs were synthesised and tested as an option for patients who are not candidates to cisplatin-based therapy...
August 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800469/immunotherapy-in-ovarian-endometrial-and-cervical-cancer-state-of-the-art-and-future-perspectives
#20
REVIEW
Jole Ventriglia, Immacolata Paciolla, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Rosa Tambaro, Daniela Califano, Simona Losito, Giosuè Scognamiglio, Sergio Venanzio Setola, Laura Arenare, Sandro Pignata, Chiara Della Pepa
The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy...
September 2017: Cancer Treatment Reviews
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