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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#1
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28623887/association-between-the-ercc1-polymorphism-and-platinum-based-chemotherapy-effectiveness-in-ovarian-cancer-a-meta-analysis
#2
Ning Tang, Dan Lyu, Yan Zhang, Haiping Liu
BACKGROUND: Ovarian cancer is a prominent public health problem which affects people all around the world. Platinum-based chemotherapy is a common treatment for ovarian cancer, however, the effectiveness of chemotherapy varies from patient to patient. The excision repair cross complementation group 1 (ERCC1) protein may mediate chemotherapy resistance. A meta-analysis was conducted to explore whether platinum-based chemotherapy effectiveness could be attributed to the ERCC1 C19007T polymorphisms...
June 17, 2017: BMC Women's Health
https://www.readbyqxmd.com/read/28623073/commentary-on-biallelic-inactivation-of-brca2-in-platinum-sensitive-metastatic-castration-resistant-prostate-cancer-cheng-hh-pritchard-cc-boyd-t-nelson-ps-montgomery-b-eur-urol-jun-2016-69-6-992-5
#3
Stephen Freedland, William Aronson
Understanding the molecular underpinnings of sensitivity to specific therapies will advance the goal of precision medicine in prostate cancer (PCa). We identified 3 patients with metastatic castration-resistant PCa (mCRPC) who achieved an exceptional response to platinum chemotherapy (not first-line treatment for PCa), despite disease progression on prior standard therapies. Using targeted next-generation sequencing on the primary and metastatic tumors, we found that all 3 patients had biallelic inactivation of BRCA2, a tumor suppressor gene critical for homologous DNA repair...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28622685/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#4
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...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620903/emerging-categories-of-disease-in-advanced-prostate-cancer-and-their-therapeutic-implications
#5
REVIEW
Rahul R Aggarwal, Felix Y Feng, Eric J Small
The treatment of advanced prostate cancer has changed significantly in the last decade, as a result of the introduction of multiple new systemic therapies that have had a positive impact on treatment outcomes. The increasing number of therapies, along with new insights into the biological underpinnings of prostate cancer, have led to a growing appreciation for the heterogeneity of the disease and an awareness of emerging subcategories that have direct therapeutic implications for the practicing clinician. In the metastatic hormone-naive setting, the extent of metastatic disease visible on scans can serve as a useful measure to guide treatment decisions; the addition of docetaxel chemotherapy to hormonal therapy has significant benefit in patients whose scans show more extensive disease...
June 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28619062/platinum-containing-compound-platinum-pyrithione-suppresses-ovarian-tumor-proliferation-through-proteasome-inhibition
#6
Hongbiao Huang, Ni Liu, Yuning Liao, Ningning Liu, Jianyu Cai, Xiaohong Xia, Zhiqiang Guo, Yanling Li, Qirong Wen, Qi Yin, Yan Liu, Qingxia Wu, Dhivya Rajakumar, Xiujie Sheng, Jinbao Liu
BACKGROUND: Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent. METHOD: MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis...
June 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28617432/bst2-confers-cisplatin-resistance-via-nf-%C3%AE%C2%BAb-signaling-in-nasopharyngeal-cancer
#7
Chun-Mei Kuang, Xiang Fu, Yi-Jun Hua, Wen-di Shuai, Zhi-Hua Ye, Yingchang Li, Qi-Hua Peng, Yi-Zhuo Li, Shuai Chen, Chao-Nan Qian, Wenlin Huang, Ran-Yi Liu
Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28614062/brca-mutations-in-the-manifestation-and-treatment-of-ovarian-cancer
#8
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...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608931/the-association-between-germline-brca2-variants-and-sensitivity-to-platinum-based-chemotherapy-among-men-with-metastatic-prostate-cancer
#9
Mark M Pomerantz, Sandor Spisák, Li Jia, Angel M Cronin, Istvan Csabai, Elisa Ledet, A Oliver Sartor, Irene Rainville, Edward P O'Connor, Zachary T Herbert, Zoltan Szállási, William K Oh, Philip W Kantoff, Judy E Garber, Deborah Schrag, Adam S Kibel, Matthew L Freedman
BACKGROUND: Breast cancer 2 (BRCA2)-associated breast and ovarian cancers are sensitive to platinum-based chemotherapy. It is unknown whether BRCA2-associated prostate cancer responds favorably to such treatment. METHODS: A retrospective analysis of a single-institution cohort of men with castration-resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate-specific antigen response to carboplatin-based chemotherapy...
June 13, 2017: Cancer
https://www.readbyqxmd.com/read/28608263/molecular-markers-of-dna-damage-and-repair-in-cervical-cancer-patients-treated-with-cisplatin-neoadjuvant-chemotherapy-an-exploratory-study
#10
Nilda E Real, Gisela N Castro, F Darío Cuello-Carrión, Claudia Perinetti, Hanna Röhrich, Niubys Cayado-Gutiérrez, Martin E Guerrero-Gimenez, Daniel R Ciocca
Neoadjuvant (or induction) chemotherapy can be used for cervical cancer patients with locally advanced disease; this treatment is followed by radical surgery and/or radiation therapy. Cisplatin is considered to be the most active platinum agent drug for this cancer, with a response rate of 20%. In order to understand how the cisplatin treatment affects the stress response, in this work, we performed an exploratory study to analyze a number of stress proteins before and after cisplatin neoadjuvant chemotherapy...
June 12, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28601656/prognostic-relevance-of-src-activation-in-stage-ii-iii-colon-cancer
#11
Julia Martinez Perez, Iker Lopez-Calderero, Carmen Saez, Marta Benavent, Maria L Limon, Reyes Gonzalez-Exposito, B Soldevilla, Maria C Riesco-Martinez, Javier Salamanca, Amancio Carnero, Rocio Garcia-Carbonero
Src belongs to a family of cytoplasmic tyrosine kinases that play a key role in tumor initiation and progression. Src activation has been associated with a more aggressive neoplastic phenotype and induces resistance to platinum agents in preclinical models. The aim of our study was to assess the prognostic and/or predictive value of Src activation in stage II-III colon cancer patients. pSrc expression was assessed in paraffin-embedded tumor samples by immunohistochemistry (phospho Y418, ab4816, Abcam). Cases were classified by staining intensity in four categories: no staining (0), weak (1+), moderate (2+) and intense (3+) staining...
June 7, 2017: Human Pathology
https://www.readbyqxmd.com/read/28599472/nucleus-accumbens-1-gadd45gip1-axis-mediates-cisplatin-resistance-through-cellular-senescence-in-ovarian-cancer
#12
Kentaro Nakayama, Munmun Rahman, Mohammed Tanjimur Rahman, Kohei Nakamura, Emi Sato, Hiroshi Katagiri, Tomoka Ishibashi, Masako Ishikawa, Kouji Iida, Sultana Razia, Noriyuki Ishikawa, Satoru Kyo
Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the bric-a-brac-tramtrack-broad complex/pox virus and zinc finger gene family, is known to serve important roles in the proliferation and growth of tumor cells, and in chemotherapy resistance. However, the underlying molecular mechanisms through which NAC1 contributes to drug resistance remain unclear. In the present study, the role of NAC1 in drug resistance in ovarian cancer was investigated. NAC1 expression was markedly negatively associated with growth arrest and DNA-damage-inducible 45γ-interacting protein 1 (GADD45GIP1) expression in ovarian cancer...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596446/reducing-uncertainty-predictors-of-stopping-chemotherapy-early-and-shortened-survival-time-in-platinum-resistant-refractory-ovarian-cancer-the-gcig-symptom-benefit-study
#13
Felicia T Roncolato, Florence Joly, Rachel O'Connell, Anne Lanceley, Felix Hilpert, Luke Buizen, Aikou Okamoto, Eriko Aotani, Sandro Pignata, Paul Donnellan, Amit Oza, Elisabeth Avall-Lundqvist, Jonathan S Berek, Florian Heitz, Amanda Feeney, Dominique Berton-Rigaud, Martin R Stockler, Madeleine King, Michael Friedlander
BACKGROUND: Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy. MATERIALS AND METHODS: This study enrolled women with PRROC before starting palliative chemotherapy...
June 8, 2017: Oncologist
https://www.readbyqxmd.com/read/28588720/synergistic-activity-of-the-histone-deacetylase-inhibitor-trichostatin-a-and-the-proteasome-inhibitor-ps-341-against-taxane-resistant-ovarian-cancer-cell-lines
#14
Xin Jin, Yong Fang, Yi Hu, Jing Chen, Wei Liu, Gang Chen, Mei Gong, Peng Wu, Tao Zhu, Shixuan Wang, Jianfeng Zhou, Hui Wang, Ding Ma, Kezhen Li
Although a combination of platinum- and taxane-based chemotherapy is recommended for at least 70% patients with ovarian cancer as treatment subsequent to surgery, the initial response to the chemotherapy is not durable and tumors become resistant. Histone deacetylase and proteasome inhibitors are novel therapeutic agents. However, the moderate antitumoral effect of the inhibitors has restricted their clinical use when used as single agents. The aim of the present study was to investigate the synergistic activity of trichostatin A (TSA) and PS-341 in ovarian cancer cells, along with the investigation of the molecular mechanisms of taxane resistance...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28588062/secondary-somatic-mutations-restoring-rad51c-and-rad51d-associated-with-acquired-resistance-to-the-parp-inhibitor-rucaparib-in-high-grade-ovarian-carcinoma
#15
Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V Tinker, Nelson N H Teng, Maria I Harrell, Michael J Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M Kass, Meghan R Sullivan, Gregory J Brunette, Kara A Bernstein, Robert L Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M O'Malley, Amit M Oza, James X Sun, Liliane Robillard, Lara Maloney, David D L Bowtell, Heidi Giordano, Matthew J Wakefield, Scott H Kaufmann, Andrew D Simmons, Thomas C Harding, Mitch Raponi, Iain A McNeish, Elizabeth M Swisher, Kevin Lin, Clare L Scott
High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC...
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28580971/a-micellar-cisplatin-prodrug-simultaneously-eliminates-both-cancer-cells-and-cancer-stem-cells-in-lung-cancer
#16
Yan-Hua Zhu, Chun-Yang Sun, Song Shen, Malik I U Khan, Yang-Yang Zhao, Yang Liu, Yu-Cai Wang, Jun Wang
Platinum-based chemotherapy as first-line treatment for lung cancers encounters insufficient selectivity, severe side effects and drug resistance in clinics. In this study, we developed an amphiphilic prodrug of cisplatin-poly(ethylene glycol)-block-polycaprolactone and demonstrated that the prodrug formed micellar nanoparticles, NPPt(IV), with an average diameter of ∼100 nm. NPPt(IV) released platinum in response to the intracellular acidic and reductive environment, and in turn induced significant anti-proliferative activity in lung cancer cells...
June 5, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28577956/clinical-outcomes-of-platinum-based-chemotherapy-according-to-t790m-mutation-status-in-egfr-positive-non-small-cell-lung-cancer-patients-after-initial-egfr-tki-failure
#17
Tatsuya Yoshida, Hiroaki Kuroda, Yuko Oya, Junichi Shimizu, Yoshitsugu Horio, Yukinori Sakao, Toyoaki Hida, Yasushi Yatabe
BACKGROUND: Emergence of the T790M point mutation in exon 20 of epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). It remains unclear whether the efficacy of platinum-doublet chemotherapy is impacted by the presence of the T790M mutation. The aim of this study is to evaluate the efficacy of platinum-doublet chemotherapy after initial EGFR-TKI failure according to the EGFR T790M in patients with advanced EGFR-mutation-positive non-small cell lung cancer (NSCLC)...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28574829/the-impact-of-epcam-expression-on-response-to-chemotherapy-and-clinical-outcomes-in-patients-with-epithelial-ovarian-cancer
#18
Shingo Tayama, Takeshi Motohara, Dashdemberel Narantuya, Chenyan Li, Koichi Fujimoto, Isao Sakaguchi, Hironori Tashiro, Hideyuki Saya, Osamu Nagano, Hidetaka Katabuchi
Epithelial ovarian cancer is a highly lethal malignancy; moreover, overcoming chemoresistance is the major challenging in treating ovarian cancer patients. The cancer stem cell (CSC) hypothesis considers CSCs to be the main culprits in driving tumor initiation, metastasis, and resistance to conventional therapy. Although growing evidence suggest that CSCs are responsible for chemoresistance, the contribution of CSC marker EpCAM to resistance to chemotherapy remains unresolved.Here we have demonstrated that ovarian cancers containing high levels of EpCAM have a significantly much lower probability of achieving overall responsive rates after first-line chemotherapy...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573914/treatment-strategies-for-dna-repair-deficient-prostate-cancer
#19
Benjamin A Teply, Emmanuel S Antonarakis
Common recurrent genetic alterations have been identified in prostate cancer through comprehensive sequencing efforts, and the prevalence of mutations in DNA repair pathway genes in patients with advanced and metastatic disease approaches 20-25%. Identification of these underlying DNA repair defects may present unique treatment opportunities for patients, both in terms of standard-of-care treatments and selected investigational agents. Areas covered: We review our current understanding of the genomic landscape of prostate cancer, with special attention to alterations in DNA repair pathway genes in metastatic castration-resistant disease...
June 12, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28567015/usp22-induces-cisplatin-resistance-in-lung-adenocarcinoma-by-regulating-%C3%AE-h2ax-mediated-dna-damage-repair-and-ku70-bax-mediated-apoptosis
#20
Aman Wang, Zhen Ning, Chang Lu, Wei Gao, Jinxiao Liang, Qiu Yan, Guang Tan, Jiwei Liu
Resistance to platinum-based chemotherapy is one of the most important reasons for treatment failure in advanced non-small cell lung cancer, but the underlying mechanism is extremely complex and unclear. The present study aimed to investigate the correlation of ubiquitin-specific peptidase 22 (USP22) with acquired resistance to cisplatin in lung adenocarcinoma. In this study, we found that overexpression of USP22 could lead to cisplatin resistance in A549 cells. USP22 and its downstream proteins γH2AX and Sirt1 levels are upregulated in the cisplatin- resistant A549/CDDP cell line...
2017: Frontiers in Pharmacology
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