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Drug resistance in melanoma

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https://www.readbyqxmd.com/read/29767233/potential-role-of-cyclin-f-mrna-expression-in-the-survival-of-skin-melanoma-patients-comprehensive-analysis-of-the-pathways-altered-due-to-cyclin-f-upregulation
#1
Maciej Gagat, Adrian Krajewski, Dariusz Grzanka, Alina Grzanka
Cyclin F is a part of the Skp, Cullin, F-box containing ligase complex. The activity of cyclin F includes cell cycle control, centrosome duplication and response to DNA damage. The cyclin F expression pattern is very similar to cyclin A, but cyclin F is an orphan cyclin without its cyclin-dependent kinase partner. There is little evidence concerning the role of cyclin F in cancer. In the present study, for the first time, we present analysis from The Cancer Genome Atlas (TCGA) data in the context of expression of cyclin F mRNA in melanoma patients...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765544/comparison-of-infectivity-and-spread-between-hsv-1-and-hsv-2-based-oncolytic-viruses-on-tumor-cells-with-different-receptor-expression-profiles
#2
Xinping Fu, Lihua Tao, Pin-Yi Wang, Timothy P Cripe, Xiaoliu Zhang
Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1. Recently, we and others have developed several HSV-2 based oncolytic viruses. During our in vitro characterization of oncolytic viruses developed from both serotypes (Baco-1 from HSV-1 and FusOn-H2 from HSV-2), we noticed there is a subpopulation of cancer cells in which both viruses could infect but only FusOn-H2 could spread from cell to cell on monolayers...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764854/preclinical-antitumor-activity-of-a-novel-anti-c-kit-antibody-drug-conjugate-against-mutant-and-wild-type-c-kit-positive-solid-tumors
#3
Tinya J Abrams, Anu Connor, Christie P Fanton, Steven B Cohen, Thomas Huber, Kathy Miller, E Erica Hong, Xiaohong Niu, Janine Kline, Marjorie Ison-Dugenny, Sarah Harris, Dana B Walker, Klaus R Krauser, Francesco Galimi, Zhen Wang, Majid Ghoddusi, Keith G Mansfield, Si Tuen Lee-Hoeflich, Jocelyn Holash, Nancy Pryer, William Kluwe, Seth A Ettenberg, William R Sellers, Emma Lees, Paul Kwon, Judith A Abraham, Siew Schleyer
PURPOSE: c-KIT overexpression is well-recognized in cancers such as GIST, SCLC, melanoma, NSCLC and AML. Treatment with the small molecule inhibitors imatinib, sunitinib and regorafenib result in resistance (c-KIT mutant tumors) or limited activity (c-KIT wildtype tumors). We selected an anti-c-KIT ADC approach to evaluate the anti-cancer activity in multiple disease models. EXPERIMENTAL DESIGN: A humanized anti-c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a non-cleavable linker (SMCC)...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29763619/targeting-the-un-differentiated-state-of-cancer
#4
Lajos V Kemeny, David E Fisher
Dedifferentation in cancer is associated with intrinsic and acquired resistance to therapies. In this issue of Cancer Cell, Tsoi et al. identify four differentiation states in melanoma and provide evidence that melanoma cells develop drug resistance through a stepwise dedifferentiation process, making them vulnerable to ferroptotic cell death-inducing compounds.
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29760678/controversial-role-of-kisspeptins-kiss-1r-signaling-system-in-tumor-development
#5
REVIEW
Federica Fratangelo, Maria Vincenza Carriero, Maria Letizia Motti
KiSS-1 was first described as a metastasis suppressor gene in malignant melanoma. KiSS-1 encodes a 145 amino-acid residue peptide that is further processed, producing the 54 amino acid metastin and shorter peptides collectively named kisspeptins (KPs). KPs bind and activate KiSS-1R (GPR54). Although the KPs system has been extensively studied for its role in endocrinology of reproductive axis in mammals, its role in cancer is still controversial. Experimental evidences show that KP system exerts an anti-metastatic effect by the regulation of cellular migration and invasion in several cancer types...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29754815/an-acquired-vulnerability-of-drug-resistant-melanoma-with-therapeutic-potential
#6
Liqin Wang, Rodrigo Leite de Oliveira, Sanne Huijberts, Evert Bosdriesz, Nora Pencheva, Diede Brunen, Astrid Bosma, Ji-Ying Song, John Zevenhoven, G Tjitske Los-de Vries, Hugo Horlings, Bastiaan Nuijen, Jos H Beijnen, Jan H M Schellens, Rene Bernards
BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance that is frequently caused by reactivation of the mitogen activated protein kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor vorinostat suppresses SLC7A11, leading to a lethal increase in the already-elevated levels of ROS in drug-resistant cells...
April 28, 2018: Cell
https://www.readbyqxmd.com/read/29753256/new-antineoplastic-agent-based-on-a-dibenzoylmethane-derivative-cytotoxic-effect-and-direct-interaction-with-dna
#7
Fernanda R Nascimento, Tiago A Moura, Jefferson V P B Baeta, Bruno C Publio, Pollyanna M F Ferreira, Anésia A Santos, Andressa A P França, Marcio S Rocha, Gaspar Diaz-Muñoz, Marisa A N Diaz
Melanoma accounts for only 4% of all skin cancers but is among the most lethal cutaneous neoplasms. Dacarbazine is the drug of choice for the treatment of melanoma in Brazil through the public health system mainly because of its low cost. However, it is an alkylating agent of low specificity and elicits a therapeutic response in only 20% of cases. Other drugs available for the treatment of melanoma are expensive, and tumor cells commonly develop resistance to these drugs. The fight against melanoma demands novel, more specific drugs that are effective in killing drug-resistant tumor cells...
May 3, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29749510/inhibition-of-endoplasmic-reticulum-stress-induced-autophagy-sensitizes-melanoma-cells-to-temozolomide-treatment
#8
Oxana Ryabaya, Anastasia Prokofieva, Dmitry Khochenkov, Ivan Abramov, Alexander Zasedatelev, Evgenia Stepanova
The incidence of malignant melanoma is increasing. The discovery of agents specifically targeting the mutated cascades has provided a good response for patients with oncogenic B-Raf proto-оncogene, serine/threonine kinase (BRAF). However, numerous studies continue to focus on novel methods of treatment to overcome acquired resistance to novel drugs. Recently, it has been revealed that inhibition of endoplasmic reticulum (ER) stress chaperon 78 kDa glucose-regulated protein 78 (GRP78) leads to down-regulation of autophagy and increased sensitivity to temozolomide (TMZ) treatment...
May 9, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29737325/the-mek1-2-inhibitor-azd6244-sensitizes-braf-mutant-thyroid-cancer-to-vemurafenib
#9
Hao Song, Jinna Zhang, Liang Ning, Honglai Zhang, Dong Chen, Xuelong Jiao, Kejun Zhang
BACKGROUND [i]BRAF[/i]V600E mutation occurs in approximately 45% of papillary thyroid cancer (PTC) cases, and 25% of anaplastic thyroid cancer (ATC) cases. Vemurafenib/PLX4032, a selective BRAF inhibitor, suppresses extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase 1/2 (MEK/ERK1/2) signaling and shows beneficial effects in patients with metastatic melanoma harboring the [i]BRAFV600E[/i] mutation. However, the response to vemurafenib is limited in BRAF-mutant thyroid cancer. The present study evaluated the effect of vemurafenib in combination with the selective MEK1/2 inhibitor AZD6244 on cell survival and explored the mechanism underlying the combined effect of vemurafenib and AZD6244 on thyroid cancer cells harboring BRAFV600E...
May 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29729495/braf-in-non-small-cell-lung-cancer-nsclc-pickaxing-another-brick-in-the-wall
#10
REVIEW
Alessandro Leonetti, Francesco Facchinetti, Giulio Rossi, Roberta Minari, Antonia Conti, Luc Friboulet, Marcello Tiseo, David Planchard
Molecular characterization of non-small cell lung cancer (NSCLC) marked an historical turning point for the treatment of lung tumors harboring kinase alterations suitable for specific targeted drugs inhibition, translating into major clinical improvements. Besides EGFR, ALK and ROS1, BRAF represents a novel therapeutic target for the treatment of advanced NSCLC. BRAF mutations, found in 1.5-3.5% of NSCLC, are responsible of the constitutive activation of mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway...
April 24, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29719603/gefitinib-or-lapatinib-with-foretinib-synergistically-induce-a-cytotoxic-effect-in-melanoma-cell-lines
#11
Ewelina Dratkiewicz, Katarzyna Pietraszek-Gremplewicz, Aleksandra Simiczyjew, Antonina Joanna Mazur, Dorota Nowak
Melanoma is an aggressive cancer type with a high mortality rate and an elevated resistance to conventional treatment. Recently, promising new tools for anti-melanoma targeted therapy have emerged including inhibitors directed against frequently overexpressed receptors of growth factors implicated in the progression of this cancer. The ineffectiveness of single-targeted therapy prompted us to study the efficacy of treatment with a combination of foretinib, a MET (hepatocyte growth factor receptor) inhibitor, and gefitinib or lapatinib, EGFR (epidermal growth factor receptor) inhibitors...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29717260/a-modified-gene-trap-approach-for-improved-high-throughput-cancer-drug-discovery
#12
Shelli M Morris, Andrew J Mhyre, Savanna S Carmack, Carrie H Myers, Connor Burns, Wenjuan Ye, Marc Ferrer, James M Olson, Richard A Klinghoffer
While advances in laboratory automation has dramatically increased throughout of compound screening efforts, development of robust cell-based assays in relevant disease models remain resource-intensive and time-consuming, presenting a bottleneck to drug discovery campaigns. To address this issue, we present a modified gene trap approach to efficiently generate pathway-specific reporters that result in a robust "on" signal when the pathway of interest is inhibited. In this proof-of-concept study, we used vemurafenib and trametinib to identify traps that specifically detect inhibition of the mitogen-activated protein kinase (MAPK) pathway in a model of BRAFV600E driven human malignant melanoma...
May 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29704617/the-role-of-small-molecule-kit-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-neoplastic-disorders
#13
REVIEW
Robert Roskoski
The Kit proto-oncogene was found as the consequence of the discovery of the feline v-kit sarcoma oncogene. Stem cell factor (SCF) is the Kit ligand and it mediates Kit dimerization and activation. The Kit receptor contains an extracellular segment that is made up of five immunoglobulin-like domains (D1/2/3/4/5), a transmembrane segment, a juxtamembrane segment, a protein-tyrosine kinase domain that contains an insert of 77 amino acid residues, and a carboxyterminal tail. Activating somatic mutations in Kit have been documented in various neoplasms including gastrointestinal stromal tumors (GIST), mast cell overexpression (systemic mastocytosis), core-binding factor acute myeloid leukemias (AML), melanomas, and seminomas...
April 25, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29692251/the-anti-malarial-drug-artesunate-blocks-wnt-%C3%AE-catenin-pathway-and-inhibits-growth-migration-and-invasion-of-uveal-melanoma-cells
#14
Lei Zheng, Jingxuan Pan
BACKGROUND: Uveal melanoma is the most common primary intraocular malignancy in adults. So far, there have been no effective targeted therapeutic agents in patients with uveal melanoma. Artesunate is a semi-synthetic derivative of artemisinin extracted from traditional Chinese medicine Artemisia annua L for treatment of severe and multidrug-resistant malaria. Besides its anti-malarial activity, artesunate is identified as an anti-cancer drug due to the inhibition of Wnt/b-catenin pathway in multiple types of cancer...
April 25, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29682512/targeting-notch-signalling-pathway-of-cancer-stem-cells
#15
REVIEW
Vandana Venkatesh, Raghu Nataraj, Gopenath S Thangaraj, Murugesan Karthikeyan, Ashok Gnanasekaran, Shanmukhappa B Kaginelli, Gobianand Kuppanna, Chandrashekrappa Gowdru Kallappa, Kanthesh M Basalingappa
Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#16
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29662054/characterising-the-phenotypic-evolution-of-circulating-tumour-cells-during-treatment
#17
Simon Chang-Hao Tsao, Jing Wang, Yuling Wang, Andreas Behren, Jonathan Cebon, Matt Trau
Real-time monitoring of cancer cells' phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as "cell signature"), without the need for isolating individual CTCs...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29657129/multi-stage-differentiation-defines-melanoma-subtypes-with-differential-vulnerability-to-drug-induced-iron-dependent-oxidative-stress
#18
Jennifer Tsoi, Lidia Robert, Kim Paraiso, Carlos Galvan, Katherine M Sheu, Johnson Lay, Deborah J L Wong, Mohammad Atefi, Roksana Shirazi, Xiaoyan Wang, Daniel Braas, Catherine S Grasso, Nicolaos Palaskas, Antoni Ribas, Thomas G Graeber
Malignant transformation can result in melanoma cells that resemble different stages of their embryonic development. Our gene expression analysis of human melanoma cell lines and patient tumors revealed that melanoma follows a two-dimensional differentiation trajectory that can be subclassified into four progressive subtypes. This differentiation model is associated with subtype-specific sensitivity to iron-dependent oxidative stress and cell death known as ferroptosis. Receptor tyrosine kinase-mediated resistance to mitogen-activated protein kinase targeted therapies and activation of the inflammatory signaling associated with immune therapy involves transitions along this differentiation trajectory, which lead to increased sensitivity to ferroptosis...
April 3, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29655680/panduratin-a-induces-protective-autophagy-in-melanoma-via-the-ampk-and-mtor-pathway
#19
Siew-Li Lai, Mohd Rais Mustafa, Pooi-Fong Wong
BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer therapeutics in recent years. Autophagy can be modulated to drive cancer cell deaths that are notoriously resistant to apoptotic-inducing drugs. In addition, autophagy has been implicated as a prosurvival mechanism in mediating cancer chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a plant-derived active compound exploits ER-stress-mediated apoptosis as its cytotoxic mechanism on melanoma...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655610/structure-based-drug-design-and-in-vitro-metabolism-study-discovery-of-n-4-methylthiophenyl-n-2-dimethyl-cyclopenta-d-pyrimidine-as-a-potent-microtubule-targeting-agent
#20
Weiguo Xiang, Shruti Choudhary, Ernest Hamel, Susan L Mooberry, Aleem Gangjee
We report a series of tubulin targeting agents, some of which demonstrate potent antiproliferative activities. These analogs were designed to optimize the antiproliferative activity of 1 by varying the heteroatom substituent at the 4'-position, the basicity of the 4-position amino moiety, and conformational restriction. The potential metabolites of the active compounds were also synthesized. Some compounds demonstrated single digit nanomolar IC50 values for antiproliferative effects in MDA-MB-435 melanoma cells...
April 4, 2018: Bioorganic & Medicinal Chemistry
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