keyword
MENU ▼
Read by QxMD icon Read
search

Drug resistance in melanoma

keyword
https://www.readbyqxmd.com/read/29155017/p-glycoprotein-mdr1-abcb1-and-breast-cancer-resistance-protein-bcrp-abcg2-affect-brain-accumulation-and-intestinal-disposition-of-encorafenib-in-mice
#1
Jing Wang, Changpei Gan, Rolf W Sparidans, Els Wagenaar, Stéphanie van Hoppe, Jos H Beijnen, Alfred H Schinkel
Encorafenib (LGX818) is a promising BRAF(V600E) inhibitor that has efficacy against metastatic melanoma. To better understand its pharmacokinetics, we studied its interactions with the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug metabolizing enzyme CYP3A. In polarized MDCK-II cells, encorafenib was efficiently transported by canine and human ABCB1 and ABCG2 and by mouse Abcg2. Upon oral administration to wild-type, Abcb1a/1b(-/-), Abcg2(-/-), and Abcb1a/1b;Abcg2(-/-) mice, encorafenib was absorbed very quickly and to very high plasma levels, but without clear changes in oral availability between the strains...
November 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29137221/anti-pancreatic-cancer-activity-of-onc212-involves-the-unfolded-protein-response-upr-and-is-reduced-by-igf1-r-and-grp78-bip
#2
Avital Lev, Amriti R Lulla, Jessica Wagner, Marie D Ralff, Joshua B Kiehl, Yan Zhou, Cyril H Benes, Varun V Prabhu, Wolfgang Oster, Igor Astsaturov, David T Dicker, Wafik S El-Deiry
Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines (N=16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29114547/predictive-factors-of-response-to-immunotherapy-a-review-from-the-spanish-melanoma-group-gem
#3
REVIEW
Enrique Espinosa, Ivan Márquez-Rodas, Ainara Soria, Alfonso Berrocal, Jose Luis Manzano, Maria Gonzalez-Cao, Salvador Martin-Algarra
Immunotherapy has become a key element in the treatment of several tumors, such as lung carcinoma and melanoma. Immunotherapy, unlike classical chemotherapy and targeted drugs, may yield long-term survival, even in patients who stop treatment due to toxicity. This fact has generated considerable excitement and a real shift in the paradigm of cancer treatment. However, only a small subset of patients benefit from immunotherapy. Survival curves show that most patients have progression of the disease in the first months after starting immunotherapy, followed by a slower decrease over the first 3 years, until curves reach a plateau...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29114545/overcoming-resistance-to-braf-inhibitors
#4
REVIEW
Imanol Arozarena, Claudia Wellbrock
The discovery of activating mutations in the serine/threonine (S/T) kinase BRAF followed by a wave of follow-up research manifested that the MAPK-pathway plays a critical role in melanoma initiation and progression. BRAF and MEK inhibitors produce an unparalleled response rate in melanoma, but it is now clear that most responses are transient, and while some patients show long lasting responses the majority progress within 1 year. In accordance with the key role played by the MAPK-pathway in BRAF mutant melanomas, disease progression is mostly due to the appearance of drug-resistance mechanisms leading to restoration of MAPK-pathway activity...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29113311/the-anti-apoptotic-bag3-protein-is-involved-in-braf-inhibitor-resistance-in-melanoma-cells
#5
Luana Guerriero, Giuseppe Palmieri, Margot De Marco, Antonio Cossu, Paolo Remondelli, Mario Capunzo, Maria Caterina Turco, Alessandra Rosati
BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumour types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumour cells and can sustain IKK-γ levels, allowing a sustained activation of NF-κB. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110248/why-target-the-tumor-stroma-in-melanoma
#6
REVIEW
James Hutchenreuther, Andrew Leask
Melanoma metastasis is fatal. Melanoma cells are often characterized by an activated extracellular signal-regulated kinase (ERK) pathway downstream of mutations in BRAF. Therapies targeting these BRAF mutations are useful for a while; however, patients ultimately develop resistance to these therapies. Recent evidence suggests that this resistance occurs when tumor cells leave their microenvironment and migrate on a stiff, activated tumor stroma; that is, this resistance is linked to the presence of an extracellular matrix reminiscent of a fibrotic micronvironment...
November 6, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29100459/braf-inhibitors-resistance-and-the-promise-of-combination-treatments-for-melanoma
#7
REVIEW
Merope Griffin, Daniele Scotto, Debra H Josephs, Silvia Mele, Silvia Crescioli, Heather J Bax, Giulia Pellizzari, Matthew D Wynne, Mano Nakamura, Ricarda M Hoffmann, Kristina M Ilieva, Anthony Cheung, James F Spicer, Sophie Papa, Katie E Lacy, Sophia N Karagiannis
Identification of mutations in the gene encoding the serine/threonine-protein kinase, BRAF, and constitutive activation of the mitogen-activated protein kinase (MAPK) pathway in around 50% of malignant melanomas have led to the development and regulatory approval of targeted pathway inhibitor drugs. A proportion of patients are intrinsically resistant to BRAF inhibitors, and most patients who initially respond, acquire resistance within months. In this review, we discuss pathway inhibitors and their mechanisms of resistance, and we focus on numerous efforts to improve clinical benefits through combining agents with disparate modes of action, including combinations with checkpoint inhibitor antibodies...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29090514/transcription-factors-as-critical-players-in-melanoma-invasiveness-drug-resistance-and-opportunities-for-therapeutic-drug-development
#8
REVIEW
Karine A Cohen-Solal, Howard L Kaufman, Ahmed Lasfar
Resistance to targeted therapy in cancer is often coupled with the acquisition of a pro-invasive phenotype by tumors cells and a highly permissive tumor microenvironment promoting drug resistance. Transcription factors are frequently shown as major points of convergence of multiple dysregulated receptors and signaling pathways in cancer. Several transcription factors are now incriminated as drivers of both drug resistance and invasiveness. We focused this review on critical transcription factors playing a causal role in both the resistance to BRAF V600E targeted therapy and the pro-invasive behavior of melanoma cells...
November 1, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29074620/the-natural-product-mensacarcin-induces-mitochondrial-toxicity-and-apoptosis-in-melanoma-cells
#9
Birte Plitzko, Elizabeth N Kaweesa, Sandra Loesgen
Mensacarcin is a highly oxygenated polyketide that was first isolated from soil-dwelling Streptomyces bacteria. It exhibits potent cytostatic properties (GI50: 0.2 μM) in almost all cell lines of the National Cancer Institute (NCI)-60 cell line screen and relatively selective cytotoxicity against melanoma cells. Moreover, its low COMPARE correlations with known standard antitumor agents indicate a unique mechanism of action. Effective therapies for managing melanoma are limited, so we sought to investigate mensacarcin's unique cytostatic and cytotoxic effects and its mode of action...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29072681/demethylzeylasteral-inhibits-cell-proliferation-and-induces-apoptosis-through-suppressing-mcl1-in-melanoma-cells
#10
Yuzu Zhao, Jiang He, Jun Li, Xingzhi Peng, Xianxing Wang, Zhen Dong, Erhu Zhao, Yaling Liu, Zonghui Wu, Hongjuan Cui
Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29061773/new-drug-combination-strategies-in-melanoma-current-status-and-future-directions
#11
REVIEW
Ahmad Najem, Mohammad Krayem, Anne Perdrix, Joseph Kerger, Ahmad Awada, Fabrice Journe, Ghanem Ghanem
Melanoma is the deadliest form of skin cancer and one of the most difficult cancers to treat. Overall, melanomas have more mutations than any other cancer type. Oncogenic mutations in c-KIT, NRAS and BRAF components of the MAPK pathway have been identified in nearly 90% of cutaneous melanoma and this information has been used to develop small molecules that inhibit their activity. Highly selective BRAF and MEK inhibitors have demonstrated impressive clinical results. However, the short duration of response, the acquired resistance in most cases and the toxicity issues support the rationale for drug combination approaches to improve the outcome of MAPK inhibitors, increase their efficacy, prevent and/or overcome resistance...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29059158/raf-inhibitor-ly3009120-sensitizes-ras-or-braf-mutant-cancer-to-cdk4-6-inhibition-by-abemaciclib-via-superior-inhibition-of-phospho-rb-and-suppression-of-cyclin-d1
#12
S-H Chen, X Gong, Y Zhang, R D Van Horn, T Yin, L Huber, T F Burke, J Manro, P W Iversen, W Wu, S V Bhagwat, R P Beckmann, R V Tiu, S G Buchanan, S-B Peng
KRAS, NRAS and BRAF mutations are among the most important oncogenic drivers in many major cancer types, such as melanoma, lung, colorectal and pancreatic cancer. There is currently no effective therapy for the treatment of RAS mutant cancers. LY3009120, a pan-RAF and RAF dimer inhibitor advanced to clinical study has been shown to inhibit both RAS and BRAF mutant cell proliferation in vitro and xenograft tumor growth in vivo. Abemaciclib, a CDK4/6-selective inhibitor, is currently in phase III studies for ER-positive breast cancer and KRAS mutant lung cancer...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29052140/prion-protein-family-contributes-to-tumorigenesis-via-multiple-pathways
#13
Xiaowen Yang, Zhijun Cheng, Lihua Zhang, Guiru Wu, Run Shi, Zhenxing Gao, Chaoyang Li
A wealth of evidence suggests that proteins from prion protein (PrP) family contribute to tumorigenesis in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), breast cancer, glioblastoma, colorectal cancer, gastric cancer, melanoma, etc. It is well documented that PrP is a biomarker for PDAC, breast cancer, and gastric cancer. However, the underlying mechanisms remain unclear. The major reasons for cancer cell-caused patient death are metastasis and multiple drug resistance, both of which connect to physiological functions of PrP expressing in cancer cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29050198/mtorc1-autophagy-regulated-mertk-in-mutant-brafv600-melanoma-with-acquired-resistance-to-braf-inhibition
#14
Gongda Xue, Reto Kohler, Fengyuan Tang, Debby Hynx, Yuhua Wang, Francesca Orso, Vincent Prêtre, Reto Ritschard, Petra Hirschmann, Peter Cron, Tim Roloff, Reinhard Dummer, Mario Mandalà, Sandrine Bichet, Christel Genoud, Alexandra G Meyer, Manuele G Muraro, Giulio C Spagnoli, Daniela Taverna, Curzio Rüegg, Taha Merghoub, Daniela Massi, Huifang Tang, Mitchell P Levesque, Stephan Dirnhofer, Alfred Zippelius, Brian A Hemmings, Andreas Wicki
BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#15
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048639/phenotype-characterization-of-human-melanoma-cells-resistant-to-dabrafenib
#16
Fabiola Gilda Cordaro, Anna Lisa De Presbiteris, Rosa Camerlingo, Nicola Mozzillo, Giuseppe Pirozzi, Ernesta Cavalcanti, Antonella Manca, Giuseppe Palmieri, Antonio Cossu, Gennaro Ciliberto, Paolo A Ascierto, Salvatore Travali, Eduardo J Patriarca, Emilia Caputo
In the present study, the phenotype of melanoma cells resistant to dabrafenib (a B-RAF inhibitor) was investigated, to shed more light on melanoma resistance to B-RAF inhibition. Melanoma cells resistant to dabrafenib were generated using 3 different cell lines, A375, 397 and 624.38, all carrying B-RAFV600E, and they were characterized by cytofluorometric analysis, Ion Torrent technology, immunofluorescence and biochemistry. All dabrafenib-resistant cells showed, in addition to a re-activation of MAPK signaling, morphological changes compared to their sensitive counterparts, accompanied by an increase in CD90 (mesenchymal marker) expression and a decrease in E-cadherin (epithelial marker) expression, suggesting an epithelial-to-mesenchymal-like phenotypic transition...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048638/reversal-effect-of-adenovirus-mediated-human-interleukin%C3%A2-24-transfection-on-the-cisplatin-resistance-of-a549-ddp-lung-cancer-cells
#17
Mingju Xu, Xioawei Tang, Jinjin Guo, Wangbang Sun, Faqing Tang
Interleukin-24 (IL-24) is a tumor-suppressor gene that has been documented in human melanoma cells. IL-24 has marked antitumor activities on various types of human cancer, but its underlying mechanism remains unclear. In the present, we investigated the effects of human IL-24 (hIL-24) on the chemotherapy resistance of lung cancer cells. The cisplatin (DDP)-resistant lung carcinoma cell line A549/DDP was subjected to adenovirus-mediated transfection with the human IL-24 gene (Ad-hIL-24). The growth-inhibitory and apoptotic effects of Ad-hIL-24 on A549/DDP cells were observed, and the expression levels of AKT, phosphorylated-AKT (p-AKT) and P-glycoprotein (P-gp) were detected...
September 26, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048432/silencing-fli-or-targeting-cd13-anpep-lead-to-dephosphorylation-of-epha2-a-mediator-of-braf-inhibitor-resistance-and-induce-growth-arrest-or-apoptosis-in-melanoma-cells
#18
Alireza Azimi, Rainer Tuominen, Fernanda Costa Svedman, Stefano Caramuta, Maria Pernemalm, Marianne Frostvik Stolt, Lena Kanter, Pedram Kharaziha, Janne Lehtiö, Carolina Hertzman Johansson, Veronica Höiom, Johan Hansson, Suzanne Egyhazi Brage
A majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29045527/braf-mutant-colorectal-cancer-prognosis-treatment-and-new-perspectives
#19
E Sanz-Garcia, G Argiles, E Elez, J Tabernero
The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant melanoma, efficacy observed with BRAF inhibitors in monotherapy in mCRC is poor...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045061/suppression-of-mapk-signaling-in-braf-activated-pten-deficient-melanoma-by-blocking-%C3%AE-catenin-signaling-in-cancer-associated-fibroblasts
#20
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
keyword
keyword
10326
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"