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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/29769198/mathematical-modeling-predicts-response-to-chemotherapy-and-drug-combinations-in-ovarian-cancer
#1
Emilia Kozłowska, Anniina Färkkilä, Tuulia Vallius, Olli Carpén, Jukka Kemppainen, Seija Grénman, Rainer Lehtonen, Johanna Hynninen, Sakari Hietanen, Sampsa Hautaniemi
Platinum-based chemotherapy constitutes the backbone of clinical care in advanced solid cancers such as high-grade serous ovarian cancer (HGSOC) and has prolonged survival of millions of cancer patients. Most of these patients, however, become resistant to chemotherapy, which generally leads to a fatal refractory disease. We present a comprehensive stochastic mathematical model and simulator approach to describe platinum resistance and standard-of-care (SOC) therapy in HGSOC. We used pre- and post-treatment clinical data, including 18F-FDG-PET/CT images, to reliably estimate the model parameters and simulate "virtual HGSOC patients...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29768183/ndrg1-disruption-alleviates-cisplatin-sodium-glycididazole-induced-dna-damage-response-and-apoptosis-in-ercc1-defective-lung-cancer-cells
#2
Lang He, Kang Liu, Xiaoshan Wang, Hong Chen, Jin Zhou, Xun Wu, Tao Liu, Yongxue Yang, Xuemei Yang, Dandan Cui, Guiqin Song, Jianguo Lei, Jun Wang
BACKGROUND: Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC). METHODS: We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa...
May 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29767464/platinum-resistant-recurrent-ovarian-cancer-with-long-survival-on-bevacizumab-and-gemcitabine
#3
Shinichi Komiyama, Tsuyoki Kugimiya, Chiaki Takeya, Rena Takahashi, Kaneyuki Kubushiro
Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin...
May 16, 2018: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/29765151/apatorsen-plus-docetaxel-versus-docetaxel-alone-in-platinum-resistant-metastatic-urothelial-carcinoma-borealis-2
#4
Jonathan E Rosenberg, Noah M Hahn, Meredith M Regan, Lillian Werner, Ajjai Alva, Saby George, Joel Picus, Robert Alter, Arjun Balar, Jean Hoffman-Censits, Petros Grivas, Richard Lauer, Elizabeth A Guancial, Christopher Hoimes, Guru Sonpavde, Constantine Albany, Mark N Stein, Tim Breen, Cindy Jacobs, Kirsten Anderson, Joaquim Bellmunt, Aly-Khan A Lalani, Sumanta Pal, Toni K Choueiri
BACKGROUND: A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy. METHODS: Multicentre, phase II study with 1:1 randomisation to apatorsen (three loading doses at 600 mg intravenous followed by weekly doses) plus docetaxel (75 mg/m2 intravenous every 21 days) (A/D) or docetaxel alone...
May 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29757875/surgery-and-platinum-etoposide-based-chemotherapy-for-the-treatment-of-epithelioid-trophoblastic-tumor
#5
Janelle Sobecki-Rausch, Abigail Winder, Kruti P Maniar, Anna V Hoekstra, Emily Berry, Karen Novak, John R Lurain
OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia that develops from chorionic-type intermediate trophoblast, simulates carcinoma, presents years after a pregnancy event, is associated with low or normal human chorionic gonadotropin levels, and is relatively resistant to chemotherapy. Our aim was to identify the role of surgery in combination with platinum/etoposide-based chemotherapy in the management of both localized and metastatic ETT...
May 4, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29756633/immunotherapy-in-head-and-neck-cancer-scientific-rationale-current-treatment-options-and-future-directions
#6
Uta Rothschild, Laurent Muller, Axel Lechner, Hans A Schlösser, Dirk Beutner, Heinz Läubli, Alfred Zippelius, Sacha I Rothschild
Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms...
May 14, 2018: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29745031/trypanosoma-cruzi-biochemical-changes-and-cell-death-induced-by-an-organometallic-platinum-based-compound
#7
M Florencia Mosquillo, Lucía Bilbao, Fabricio Hernández, Florencia Tissot, Dinorah Gambino, Beatriz Garat, Leticia Pérez-Díaz
Chagas disease is an endemic illness in Latin America caused by the parasite Trypanosoma cruzi. Current chemotherapies are old and inadequate, and the emergence of drug resistant strains underscores the need of new drugs. Platinum-based complexes have been shown to be a promising approach against parasitic diseases. In this work, the effect of 1,1'-bis(diphenylphosphino)ferrocene pyridine-2-thiolate-1-oxide Pt(II) hexafluorophosphate, Pt-dppf-mpo, was studied on T. cruzi. A promising anti-trypanosomal activity was determined for the CL Brener strain with a low cytotoxicity determined using in vitro cultured mammal cells...
May 9, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29733308/therapy-testing-in-a-spheroid-based-3d-cell-culture-model-for-head-and-neck-squamous-cell-carcinoma
#8
Jan Hagemann, Christian Jacobi, Sabine Gstoettner, Christian Welz, Sabina Schwenk-Zieger, Roland Stauber, Sebastian Strieth, Julian Kuenzel, Philipp Baumeister, Sven Becker
Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood...
April 20, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29730234/microfocus-x-ray-fluorescence-mapping-of-tumour-penetration-by-an-organo%C3%A2-osmium-anticancer-complex
#9
Carlos Sanchez-Cano, Isolda Romero-Canelón, Kalotina Geraki, Peter J Sadler
Microfocus synchrotron x-ray fluorescence (SXRF) imaging focussed on detection of the Os LIII edge shows that the organo‑osmium metallodrug candidate [(ŋ6 -p-cym)Os(Azpy-NMe2 )I]+ (p-cym = p-cymene, Azpy-NMe2  = 2-(p-([dimethylamino]phenylazo)pyridine)) [1] penetrates efficiently into the interior of A2780 human ovarian cancer cell spheroids, a model for a solid tumour. The accompanying changes in Zn and Ca distribution suggest that the complex causes nuclear damage and initiates signalling events for cell death, consistent with findings for cultured cancer cell monolayers...
April 25, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29729664/complete-response-to-orally-administered-melphalan-in-malignant-pleural-effusion-from-an-occult-female-genital-organ-primary-neoplasm-with-brca1-2-mutations-a-case-report
#10
Frank S Fan, Chung-Fan Yang
BACKGROUND: Definite diagnosis of metastasis from unknown primary depends on a comprehensive immunohistochemical investigation of tumor specimen. Accurate identification of the origin site usually helps a lot in choosing the most appropriate treatment. Molecular characterization provides more chance of a cure. Echoing modern medical development, BRCA1/2 mutations have been correlated with high efficiency of poly(adenosine diphosphate-ribose) polymerase inhibitors in ovarian cancer. While a previous case report demonstrated a surprising cure of platinum-resistant ovarian cancer with BRCA2 mutation by orally administered melphalan...
May 6, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29726094/role-of-long-non-coding-rna-in-drug-resistance-in-non-small-cell-lung-cancer
#11
REVIEW
Leirong Wang, Leina Ma, Fei Xu, Wenxin Zhai, Shenghua Dong, Ling Yin, Jia Liu, Zhuang Yu
Lung cancer is the leading cause of cancer-associated death, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Many drugs have been used to treat NSCLC in order to improve patient prognosis. Platinum-based chemotherapy is the first-line treatment for locally advanced or metastatic patients. For patients with activating EGFR mutations, tyrosine kinase inhibitors are the best treatment choice. NSCLC initially exhibits an excellent response to treatment; however, acquired resistance has been observed in many patients, leading to ineffective treatment...
May 3, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29718881/histologic-transformation-from-adenocarcinoma-to-both-small-cell-lung-cancer-and-squamous-cell-carcinoma-after-treatment-with-gefitinib-a-case-report
#12
Yufeng Yao, Zhouyu Zhu, Yimin Wu, Ying Chai
RATIONALE: In the past decade, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment had been an important therapy for treating advanced EGFR-mutated lung cancer patients. However, a large number of these patients with EGFR-TKIs treatment always acquired resistance to these drugs in one year. The histologic transformation is an important resistance mechanism. PATIENT CONCERNS: Here we reported a 41-year-old man with EGFR-mutated lung adenocarcinoma and he showed histologic transformation to both small-cell lung cancer (SCLC) and squamous cell carcinoma (SCC) after treatment of gefitinib...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29702285/brief-report-afatinib-and-cetuximab-in-four-patients-with-egfr-exon-20-insertion-positive-advanced-non-small-cell-lung-cancer
#13
Bianca van Veggel, Adrianus J de Langen, Sayed Hashemi, Kim Monkhorst, Daniëlle A M Heideman, Erik Thunnissen, Egbert F Smit
INTRODUCTION: Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-9% of EGFR mutated non-small-cell lung cancer (NSCLC). Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses. METHODS: Four patients with EGFR exon 20 insertion positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250-500 mg/m2 every two weeks...
April 24, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29695695/-increase-in-bacterial-resistance-to-antibiotics-after-cancer-therapy-with-platinum-based-drugs
#14
V A Chistyakov, E V Prazdnova, M S Mazanko, M N Churilov, V K Chmyhalo
The use of platinum-based anticancer drugs is limited by both their side effects and their effect on normal microflora's metagenome. Drugs that possess mutagenic and genotoxic properties may cause mutations in microbial genomes that contribute to the emergence of resistance to antimicrobial preparations and the development of complications after chemotherapy. The effects of cisplatin and oxaliplatin on microorganisms were studied using bacterial biosensors - E. coli strains MG1655 pKatG-lux, which reacts to the generation of hydrogen peroxide; MG1655 pSoxS-lux, which reacts to the superoxide anion radical; and the MG1655 pColD-lux strain, which detects DNA damage...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29693178/identifying-genes-as-potential-prognostic-indicators-in-patients-with-serous-ovarian-cancer-resistant-to-carboplatin-using-integrated-bioinformatics-analysis
#15
Shi-Jie Zhan, Bin Liu, Hua Linghu
Serous ovarian cancer (SOC) accounts for >50% of all epithelial ovarian cancers. However, patients with SOC present with various degrees of response to platinum‑based chemotherapy and, thus, their survival may differ. The present study aimed to identify the candidate genes involved in the carcinogenesis and drug resistance of SOC by analyzing the microarray datasets GDS1381 and GDS3592. GDS1381 and GDS3592 were downloaded from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/gds/). A total of 219 differentially expressed genes (DEGs) were identified...
April 19, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29676505/differential-reactivity-of-metal-binding-domains-of-copper-atpases-towards-cisplatin-and-colocalization-of-copper-and-platinum
#16
Tiantian Fang, Yao Tian, Siming Yuan, Yaping Sheng, Arnesano Fabio, Giovanni Natile, Yangzhong Liu
P-type ATPases, including MNK and WLN proteins, are responsible for active Cu efflux. These ATPases are also associated with resistance to cisplatin. In this work, we produced different metal-binding domains (MBDs) of ATPase (9 out of 12 domains), and compared their reactivity towards cisplatin. The reaction rates of the MBDs can be largely different; the reaction of MNK6 is about 6 times faster than that of WLN2. Copper coordination favors the platination of the MBDs to different extents. The rate of platination was generally grater for holo-MBDs than for apo-MBDS (particularly in the case of WLN4 and WLN2), however it was negligibly affected in the case of MNK6...
April 20, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29656750/afatinib-in-heavily-pretreated-advanced-nsclc-patients-who-progressed-following-prior-gefitinib-or-erlotinib-compassionate-use-program-in-korea
#17
Moon Ki Choi, Jin Seok Ahn, Young-Chul Kim, Byoung Chul Cho, In-Jae Oh, Sang-We Kim, Jong Seok Lee, Joo-Hang Kim, Myung-Ju Ahn, Keunchil Park
INTRODUCTION: Afatinib, an irreversible ErbB family blocker, approved for first-line treatment of epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC). This study investigated experience of afatinib within a compassionate use program (CUP). METHODS: The afatinib CUP was an open-label, multicenter, single-arm program in Korea. We enrolled patients with stage IV NSCLC and who had received at least one line of previous cytotoxic chemotherapy and previous EGFR TKI treatment with either an EGFR mutation or documented clinical benefit...
May 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29650143/perioperative-immunotherapy-in-muscle-invasive-bladder-cancer-and-upper-tract-urothelial-carcinoma
#18
REVIEW
Min Yuen Teo, Jonathan E Rosenberg
Neoadjuvant chemotherapy improves survival in patients with muscle-invasive bladder cancer. However, a significant proportion of patients are ineligible for cisplatin owing to renal impairment or other medical comorbidities. The introduction of anti-programmed cell death protein 1/programmed death-ligand 1(PD1/PD-L1) checkpoint inhibitors has redefined the therapeutic landscape for platinum-resistant urothelial cancers; their clinical efficacy and favorable toxicity render these agents attractive therapeutic options either as monotherapy or in combination with other agents in earlier disease states, including muscle-invasive disease...
May 2018: Urologic Clinics of North America
https://www.readbyqxmd.com/read/29644491/update-on-parp-inhibitors-in-breast-cancer
#19
REVIEW
Alexandra S Zimmer, Mitchell Gillard, Stanley Lipkowitz, Jung-Min Lee
The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer...
April 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29644000/cdk4-6-inhibition-as-maintenance-and-combination-therapy-for-high-grade-serous-ovarian-cancer
#20
Mangala Iyengar, Patrick O'Hayer, Alex Cole, Tara Sebastian, Kun Yang, Lan Coffman, Ronald J Buckanovich
High grade serous ovarian cancer (HGSOC) is a disease with a high relapse rate and poor overall survival despite good initial responses to platinum-based therapy. Cell cycle inhibition with targeted CDK4/6 inhibitors is a new therapeutic approach showing promise as a maintenance therapy in cancer. As multiple genes in the CDK4/6 pathway are commonly mutated or dysregulated in ovarian cancer, we evaluated the efficacy of the CDK4/6 inhibitor Ribociclib alone, in combination with chemotherapy, and as maintenance therapy in several models of HGSOC...
March 20, 2018: Oncotarget
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