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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/29307819/absence-of-rev3l-promotes-p53-regulated-cancer-cell-metabolism-in-cisplatin-treated-lung-carcinoma-cells
#1
Linghao Kong, Michael M Murata, Michelle A Digman
Lung cancer is one of the deadliest cancers in the world because of chemo-resistance to the commonly used cisplatin-based treatments. The use of low fidelity DNA polymerases in the translesional synthesis (TLS) DNA damage response pathway that repairs lesions caused by cisplatin also presents a mutational carcinogenic burden on cells that needs to be regulated by the tumor suppressor protein p53. However, there is much debate over the roles of the reversionless 3-like (REV3L) protein responsible for TLS and p53 in regulating cancer cell metabolism...
January 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#2
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29296209/the-prognostic-value-of-ki67-in-ovarian-high-grade-serous-carcinoma-an-11-year-cohort-study-of-chinese-patients
#3
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 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288364/mirna-signature-predicts-the-response-of-patients-with-advanced-lung-adenocarcinoma-to-platinum-based-treatment
#4
Xiaoyue Xu, Shaorong Yu, Wenbo Sun, Xiaobing Qin, Yan Chen, Leilei Zhou, Rui Lou, Shuchen Dong, Bo Shen, Jianzhong Wu, Jialan Zang, Haixia Cao, Meiqi Shi, Qin Zhang, Jifeng Feng
BACKGROUND: Accumulating literature proved that miRNAs can regulate the sensitivity of platinum and act as a promising candidate to predict the response of patients with lung adenocarcinoma to chemotherapy. However, most studies on miRNAs were restricted to in vitro experiments. This study aimed to evaluate whether miRNAs alone or in combination (miRNA signature) can act as predictive biomarkers of platinum-based chemotherapy in patients with lung adenocarcinoma. METHODS: Eight miRNAs that most probably predict the efficacy of platinum were screened in 111 tumor tissues of lung adenocarcinoma...
December 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29277822/bevacizumab-added-to-moderate-dose-chemotherapy-for-refractory-uterine-cancer
#5
Howard W Bruckner, Daniel Gurell, Azriel Hirschfeld
BACKGROUND/AIM: Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs. PATIENTS AND METHODS: Eligible patients (n=9) had high-grade endometrial tumors and had failed standard chemotherapy...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29258812/evaluating-bevacizumab-in-combination-with-folfiri-after-the-failure-of-platinum-etoposide-regimen-in-patients-with-advanced-poorly-differentiated-neuroendocrine-carcinoma-the-prodige-41-bevanec-randomized-phase-ii-study
#6
Thomas Walter, David Malka, Olivia Hentic, Catherine Lombard-Bohas, Karine Le Malicot, Denis Smith, Aurélie Ferru, Eric Assenat, Guillaume Cadiot, Astrid Lievre, Jean-Emmanuel Kurtz, Laetitia Dahan, Olivier Dubreuil, Vincent Hautefeuille, Céline Lepere, Alice Gangloff, Farid Elhajbi, Romain Coriat, Guillaume Roquin, Nadia Bouarioua, Victoire Granger, Jean-Yves Scoazec, Côme Lepage
INTRODUCTION: Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment. AIM: PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC...
December 6, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29250200/update-on-squamous-cell-carcinoma-of-the-head-and-neck-asco-annual-meeting-2017
#7
REVIEW
Teresa Magnes, Alexander Egle, Richard Greil, Thomas Melchardt
At the annual ASCO meeting clinically relevant data concerning the management of advanced head and neck cancer that will influence clinical practice in the future were presented. Chemoradiation with high-dose cisplatin remains the mainstay of treatment for patients with locally advanced squamous cell head and neck cancer. Adjuvant therapy with afatinib following chemoradiation failed to show clinical benefit. The combination of bevacizumab with platinum-based chemotherapy improved progression-free survival but did not lead to a significant difference in overall survival compared to chemotherapy alone...
2017: Memo
https://www.readbyqxmd.com/read/29248998/measuring-what-matters-most-validation-of-the-measure-of-ovarian-symptoms-and-treatment-a-patient-reported-outcome-measure-of-symptom-burden-and-impact-of-chemotherapy-in-recurrent-ovarian-cancer
#8
Madeleine T King, Martin R Stockler, Rachel L O'Connell, Luke Buizen, Florence Joly, Anne Lanceley, Felix Hilpert, Aikou Okamoto, Eriko Aotani, Jane Bryce, Paul Donnellan, Amit Oza, Elisabeth Avall-Lundqvist, Jonathan S Berek, Jalid Sehouli, Amanda Feeney, Dominique Berton-Rigaud, Daniel S J Costa, Michael L Friedlander
PURPOSE: Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit. METHODS: GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with ≥ 3 lines of prior chemotherapy (PPS-ROC ≥ 3)...
December 16, 2017: Quality of Life Research
https://www.readbyqxmd.com/read/29247488/oxaliplatin-resistance-in-colorectal-cancer-cells-is-mediated-via-activation-of-abcg2-to-alleviate-er-stress-induced-apoptosis
#9
Hsi-Hsien Hsu, Ming-Cheng Chen, Rathinasamy Baskaran, Yueh-Min Lin, Cecilia Hsuan Day, Yi-Jiun Lin, Chuan-Chou Tu, Viswanadha Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Oxaliplatin (OXA), is a third generation platinum drug used as first-line chemotherapy in colorectal cancer (CRC). Cancer cells acquires resistance to anti-cancer drug and develops resistance. ATP-binding cassette (ABC) drug transporter ABCG2, one of multidrug resistance (MDR) protein which can effectively discharge a wide spectrum of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular concentration of these drugs. Role of ABCG2 and plausible molecular signaling pathways involved in Oxaliplatin-Resistant (OXA-R) colon cancer cells was evaluated in the present study...
December 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29243164/effects-of-exercise-during-chemotherapy-on-chemotherapy-induced-peripheral-neuropathy-a-multicenter-randomized-controlled-trial
#10
Ian R Kleckner, Charles Kamen, Jennifer S Gewandter, Nimish A Mohile, Charles E Heckler, Eva Culakova, Chunkit Fung, Michelle C Janelsins, Matthew Asare, Po-Ju Lin, Pavan S Reddy, Jeffrey Giguere, Jeffrey Berenberg, Shelli R Kesler, Karen M Mustian
PURPOSE: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms...
December 14, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29240605/platelet-derived-growth-factor-d-is-a-prognostic-biomarker-and-is-associated-with-platinum-resistance-in-epithelial-ovarian-cancer
#11
Mengjun Zhang, Tianbo Liu, Bairong Xia, Chunyan Yang, Siyu Hou, Wanlin Xie, Ge Lou
OBJECTIVE: This study aimed to investigate whether platelet-derived growth factor D (PDGF-D) is a prognostic biomarker and is associated with platinum resistance in epithelial ovarian cancer, which has not been studied by others previously. METHODS: In this study, we detected expression of PDGF-D in ovarian cancer tissues through immunohistochemistry and Western blotting. Furthermore, we analyzed the association between PDGF-D expression and clinicopathological features including prognosis in epithelial ovarian cancer...
December 13, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29232464/treatment-of-recurrent-ovarian-cancer
#12
S Pignata, S C Cecere, A Du Bois, P Harter, F Heitz
Despite optimal surgery and appropriate first-line chemotherapy, ∼70%-80% of patients with epithelial ovarian cancer will develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29231057/a-critical-review-on-ramucirumab-in-the-treatment-of-advanced-urothelial-cancer
#13
Panagiotis J Vlachostergios, Aileen Lee, Charlene Thomas, Ryan Walsh, Scott T Tagawa
Advanced urothelial cancer (UC) is a lethal disease despite current advances in systemic therapy, including platinum chemotherapy combinations and immune checkpoint inhibition. Tumor angiogenesis is involved in UC growth and metastatic progression. Proangiogenic signaling through the VEGFR is a key process in UC with prognostic significance. Targeting of VEGFR2 with the monoclonal antibody ramucirumab has been tested in various different tumor types. In this review, we discuss the development of the drug in the context of its preclinical and clinical use with a focus on UC...
December 12, 2017: Future Oncology
https://www.readbyqxmd.com/read/29230006/platinum-sensitivity-in-metastatic-prostate-cancer-does-histology-matter
#14
Michael S Humeniuk, Rajan T Gupta, Patrick Healy, Megan McNamara, Sundhar Ramalingam, Michael Harrison, Daniel George, Tian Zhang, Yuan Wu, Andrew J Armstrong
BACKGROUND: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. METHODS: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent...
December 11, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29229600/genomic-and-epigenomic-signatures-in-ovarian-cancer-associated-with-re-sensitization-to-platinum-drugs
#15
Fang Fang, Horacio Cardenas, Hao Huang, Guanglong Jiang, Susan M Perkins, Chi Zhang, Harold N Keer, Yunlong Liu, Kenneth P Nephew, Daniela Matei
DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer (OC). In this study, we elucidated an epigenetic signature associated with platinum drug re-sensitization that may offer utility in predicting the outcomes of patients who are co-administered a DNA methyltransferase inhibitror. The OC specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant OC who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard of care chemotherapy regimen selected by the treating physician...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228656/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#16
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response. 192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228641/brca-mutations-in-the-manifestation-and-treatment-of-ovarian-cancer
#17
REVIEW
Zimin Pan, Xing Xie
BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29192345/transporter-mediated-interaction-between-platinum-drugs-and-sorafenib-at-the-cellular-level
#18
Verena Schneider, Selim Chaib, Claudia Spanier, Mandy Knapp, Violeta Moscvin, Laura Scordovillo, Alessandra Ewertz, Ulrich Jaehde, Ganna V Kalayda
Combining the multikinase inhibitor sorafenib with the platinum-based chemotherapy of solid tumors was expected to improve treatment outcome. However, in many clinical trials, no benefit from sorafenib addition to the platinum-containing regimen could be demonstrated. Moreover, in some studies, decreased survival of ovarian cancer patients as well as non-small cell lung cancer patients with squamous cell histology was observed. The aim of this study was to investigate the cellular mechanisms of the pharmacological interaction between platinum drugs and sorafenib in different cancer cell lines...
November 30, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29187901/mutational-landscape-of-cfdna-identifies-distinct-molecular-features-associated-with-therapeutic-response-to-first-line-platinum-based-doublet-chemotherapy-in-patients-with-advanced-nsclc
#19
Tao Jiang, Xuefei Li, Jianfei Wang, Chunxia Su, Wenbo Han, Chao Zhao, Fengying Wu, Guanghui Gao, Wei Li, Xiaoxia Chen, Jiayu Li, Fei Zhou, Jing Zhao, Weijing Cai, Henghui Zhang, Bo Du, Jun Zhang, Shengxiang Ren, Caicun Zhou, Hui Yu, Fred R Hirsch
Rationale To investigate whether the mutational landscape of circulating cell-free DNA (cfDNA) could predict and dynamically monitor the response to first-line platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods Eligible patients were included and blood samples were collected from a phase III trial. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment in a 1.15M size panel covering exon regions of 1,086 genes. Molecular mutational burden (MMB) was calculated to investigate the relationship between molecular features of cfDNA and response to chemotherapy...
2017: Theranostics
https://www.readbyqxmd.com/read/29185392/immunotherapy-in-head-and-neck-cancer-evidence-and-perspectives
#20
Alicia Tosoni, Enrico Franceschi, Ernesto Pasquini, Andrea Lanese, Elisa Donini, Maria Pia Foschini, Danilo Dall'Olio, Alba A Brandes
Head and neck squamous cell carcinomas evade immune response through multiple immunologic resistance mechanisms. Two of the most commonly involved checkpoint inhibitory mechanisms are CTLA-4 and PD-1/PD-L1, which act at earlier and later stages of immune response to tumors. Pembrolizumab and nivolumab are PD-1 antibodies that interrupt the immunosuppressive pathway of inhibitory checkpoints, which are used by tumor cells to prevent immune reaction. Both recently gained US FDA approval for the treatment of patients with recurrent or metastatic head and neck cancer with disease progression during or following platinum containing chemotherapy...
December 2017: Immunotherapy
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