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Kinase targeting and clear cell carcinoma

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https://www.readbyqxmd.com/read/28061473/immunotherapy-incorporation-in-the-evolving-paradigm-of-renal-cancer-management-and-future-prospects
#1
Kenneth G Liu, Sorab Gupta, Sanjay Goel
Significant progress has been made in the management of renal cell carcinoma (RCC) during the last few decades. In early stage, localized disease, surgical resection remains the modality of choice, with no therapeutic interventions as options for post-operative therapy other than simple observation and clinical surveillance. However, treatment options in the advanced or metastatic setting are increasing at a dizzying pace, initially with cytokine therapy, then with the increased availability of targeted therapy including novel small-molecule inhibitors of receptor tyrosine kinases and monoclonal antibodies targeting novel proteins, establishing them as the current standard of care...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28059107/single-cell-time-lapse-analysis-reveals-that-podoplanin-enhances-cell-survival-and-colony-formation-capacity-of-squamous-cell-carcinoma-cells
#2
Tomoyuki Miyashita, Youichi Higuchi, Motohiro Kojima, Atsushi Ochiai, Genichiro Ishii
Tumor initiating cells (TICs) are characterized by high clonal expansion capacity. We previously reported that podoplanin is a TIC-specific marker for the human squamous cell carcinoma cell line A431. The aim of this study is to explore the molecular mechanism underlying the high clonal expansion potential of podoplanin-positive A431cells using Fucci imaging. Single podoplanin-positive cells created large colonies at a significantly higher frequency than single podoplanin-negative cells, whereas no difference was observed between the two types of cells with respect to cell cycle status...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28035577/c-met-in-chromophobe-renal-cell-carcinoma
#3
Franziska Erlmeier, Philipp Ivanyi, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Wilko Weichert, Sandra Steffens
c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/27927774/autophagy-inhibition-enhances-sunitinib-efficacy-in-clear-cell-ovarian-carcinoma
#4
Lindsay DeVorkin, Matthew Hattersley, Paul Kim, Jenna Ries, Jaeline Spowart, Michael S Anglesio, Samuel M Levi, David G Huntsman, Ravi K Amaravadi, Jeffrey D Winkler, Anna V Tinker, Julian J Lum
: Clear cell ovarian carcinoma (CCOC) is an aggressive form of epithelial ovarian cancer that exhibits low response rates to systemic therapy and poor patient outcomes. Multiple studies in CCOC have revealed expression profiles consistent with increased hypoxia, and our previous data suggests that hypoxia is correlated with increased autophagy in CCOC. Hypoxia-induced autophagy is a key factor promoting tumor cell survival and resistance to therapy. Recent clinical trials with the molecular-targeted receptor tyrosine kinase (RTK) inhibitor sunitinib have demonstrated limited activity...
December 7, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27909994/cabozantinib-a-review-in-advanced-renal-cell-carcinoma
#5
Zaina T Al-Salama, Gillian M Keating
The multiple tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx™) is approved in the USA for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the EU, cabozantinib is indicated for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. In adults with advanced or metastatic clear-cell RCC who had previously received VEGF receptor (VEGFR) TKIs, progression-free survival (PFS) and overall survival (OS) were significantly prolonged in patients who received oral cabozantinib versus oral everolimus in the pivotal METEOR trial...
December 2016: Drugs
https://www.readbyqxmd.com/read/27906674/nuclear-localization-of-the-ck2%C3%AE-subunit-correlates-with-poor-prognosis-in-clear-cell-renal-cell-carcinoma
#6
Maj Rabjerg, Barbara Guerra, Aida Oliván-Viguera, Minne Line Nedergaard Mikkelsen, Ralf Köhler, Olaf-Georg Issinger, Niels Marcussen
Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905110/distinct-molecular-landscapes-between-endometrioid-and-non-endometrioid-uterine-carcinomas
#7
Nathaniel L Jones, Joanne Xiu, Sudeshna Chatterjee-Paer, Alexandre Buckley de Meritens, William M Burke, Ana I Tergas, Jason D Wright, June Y Hou
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and non-endometrioid based on histo-pathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27904651/sunitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma
#8
REVIEW
Thomas A Schmid, Martin E Gore
Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27904650/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#9
REVIEW
Jose Manuel Ruiz-Morales, Daniel Y C Heng
The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI)...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27834463/gene-expression-profile-of-renal-cell-carcinomas-after-neoadjuvant-treatment-with-sunitinib-new-pathways-revealed
#10
Carlos Dzik, Sabrina T Reis, Nayara I Viana, Glauber Brito, Isis Paloppi, Willian Nahas, Miguel Srougi, Katia R M Leite
BACKGROUND: In renal cell carcinoma (RCC) of the clear cell type, inactivity of the VHL gene induces overexpression of HIF1 α and its targets, the tyrosine kinase receptors, promoting RCC development and progression. The discovery of tyrosine kinase inhibitors (TKIs) changed the treatment of these tumors. Other molecular pathways involved in the TKI mechanisms of action have not been described in the literature. The aim of our study was to elucidate alternative mechanisms of action of sunitinib in tumor tissue after neoadjuvant treatment of RCC...
November 1, 2016: International Journal of Biological Markers
https://www.readbyqxmd.com/read/27827315/mirna-487a-promotes-proliferation-and-metastasis-in-hepatocellular-carcinoma
#11
Rui-Min Chang, Shuai Xiao, Xiong Lei, Hao Yang, Feng Fang, Lian-Yue Yang
PURPOSE: Hepatocellular carcinoma (HCC) harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. However, the mechanisms for metastasis and recurrence remain incompletely clear. This study aimed to investigate the role of hsa-miR-487a (miR-487a) in promoting the proliferation and metastasis of HCC and to elucidate the underlying molecular mechanisms. EXPERIMENTAL DESIGN: 198 HCC samples were analyzed for association between miR-487a expression and patient clinicopathological features and prognosis...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27798955/inhibition-of-src-family-kinases-reduces-myeloid-derived-suppressor-cells-in-head-and-neck-cancer
#12
Liang Mao, Wei-Wei Deng, Guang-Tao Yu, Lin-Lin Bu, Jian-Feng Liu, Si-Rui Ma, Lei Wu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
SRC family kinases (SFKs), a group of nonreceptor tyrosine kinases, modulate multiple cellular functions, such as cell proliferation, differentiation and metabolism. SFKs display aberrant activity in progressive stages of human cancers. However, the precise role of SFKs in the head and neck squamous cell carcinoma (HNSCC) signaling network is far from clear. In this study, we found that the inhibition of SFKs activity by dasatinib effectively reduced the tumor size and population of MDSCs in the HNSCC mouse model...
October 31, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27738339/mir-99b-5p-expression-and-response-to-tyrosine-kinase-inhibitor-treatment-in-clear-cell-renal-cell-carcinoma-patients
#13
Magdalena Lukamowicz-Rajska, Christiane Mittmann, Michael Prummer, Qing Zhong, Jens Bedke, Jörg Hennenlotter, Arnulf Stenzl, Axel Mischo, Svenja Bihr, Manuela Schmidinger, Ursula Vogl, Iris Blume, Christoph Karlo, Peter Schraml, Holger Moch
A number of treatments targeting VEGF or mTOR pathways have been approved for metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority of patients show disease progression after first line therapy with a very low rate of complete or long-term responders. It has been shown that miRs may play a role in prediction of treatment response in various cancer types. The aim of our study was to identify a miR signature predictive for RCC patients' response to antiangiogenic tyrosine kinase inhibitor (TKI) treatment in the first line therapy...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27716285/safety-pharmacokinetics-and-antitumor-properties-of-anlotinib-an-oral-multi-target-tyrosine-kinase-inhibitor-in-patients-with-advanced-refractory-solid-tumors
#14
Yongkun Sun, Wei Niu, Feng Du, Chunxia Du, Shuting Li, Jinwan Wang, Li Li, Fengqing Wang, Yu Hao, Chuan Li, Yihebali Chi
BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. METHODS: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1)...
October 4, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27684973/morphologic-molecular-and-taxonomic-evolution-of-renal-cell-carcinoma-a-conceptual-perspective-with-emphasis-on-updates-to-the-2016-world-health-organization-classification
#15
Aaron M Udager, Rohit Mehra
Molecular and morphologic interrogation has driven a much-needed reexamination of renal cell carcinoma (RCC). Indeed, the recently released 2016 World Health Organization classification now recognizes 12 distinct RCC subtypes, as well as several other emerging/provisional RCC entities. From a clinical perspective, accurate RCC classification may have important implications for patients and their families, including prognostic risk stratification, targeted therapeutics selection, and identification for genetic testing...
October 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27602218/gli2-expression-levels-in-radical-nephrectomy-specimens-as-a-predictor-of-disease-progression-in-patients-with-metastatic-clear-cell-renal-cell-carcinoma-following-treatment-with-sunitinib
#16
Junya Furukawa, Hideaki Miyake, Masato Fujisawa
The aim of the present study was to investigate the role of the Hedgehog signaling pathway in the progression of metastatic clear cell renal cell carcinoma (m-ccRCC) as well as the molecular targets of sunitinib, an inhibitor of multiple tyrosine kinases. A total of 39 patients subjected to radical nephrectomy who were diagnosed with m-ccRCC and were subsequently treated with sunitinib were enrolled in the present study. The expression levels of the Hedgehog signaling proteins (GLI1, GLI2, cyclin D1, cyclin E and transforming growth factor-β) and major molecular targets of sunitinib [vascular endothelial growth factor receptor (VEGFR)-1 and -2, and platelet-derived growth factor receptor-α and -β] in primary RCC specimens were assessed by immunohistochemical staining...
September 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27574806/kinase-gene-expression-profiling-of-metastatic-clear-cell-renal-cell-carcinoma-tissue-identifies-potential-new-therapeutic-targets
#17
Pooja Ghatalia, Eddy S Yang, Brittany N Lasseigne, Ryne C Ramaker, Sara J Cooper, Dongquan Chen, Sunil Sudarshan, Shi Wei, Arjun S Guru, Amy Zhao, Tiffiny Cooper, Deborah L Della Manna, Gurudatta Naik, Richard M Myers, Guru Sonpavde
Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR) and mammalian target of rapamycin (mTOR) improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC), but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T), matched normal kidney (N) and metastatic tumor tissue (M) may assist in identifying drivers of metastasis and prioritizing therapeutic targets...
2016: PloS One
https://www.readbyqxmd.com/read/27490806/medical-treatment-of-renal-cancer-new-horizons
#18
REVIEW
Basma Greef, Tim Eisen
Renal cell carcinoma (RCC) makes up 2-3% of adult cancers. The introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in the mid-2000s radically changed the management of RCC. These targeted treatments superseded immunotherapy with interleukin-2 and interferon. The pendulum now appears to be shifting back towards immunotherapy, with the evidence of prolonged overall survival of patients with metastatic RCC on treatment with the anti-programmed cell death 1 ligand monoclonal antibody, nivolumab...
August 23, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27461605/chemotherapy-for-advanced-non-small-cell-lung-cancer-with-a-focus-on-squamous-cell-carcinoma
#19
REVIEW
Kozo Kuribayashi, Norihiko Funaguchi, Takashi Nakano
Lung cancers are broadly divided into small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and the treatments for each differ. NSCLC includes squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and others. However, because there is little difference in treatment efficacy between these histological types, they have collectively been treated as a single entity. Cytotoxic anti-cancer agents, mainly platinum-based drugs, are the first-line treatment for unresectable advanced NSCLC, and the standard therapy is combination chemotherapy with two drugs, usually involving one platinum-based and one unrelated cytotoxic drug...
April 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/27431021/nanotechnology-combined-therapy-tyrosine-kinase-bound-gold-nanorod-and-laser-thermal-ablation-produce-a-synergistic-higher-treatment-response-of-renal-cell-carcinoma-in-a-murine-model
#20
James Liu, Caleb Abshire, Connor Carry, Andrew B Sholl, Sree Harsha Mandava, Amrita Datta, Manish Ranjan, Cameron Callaghan, Donna V Peralta, Kristen S Williams, Weil R Lai, Asim B Abdel-Mageed, Matthew Tarr, Benjamin R Lee
OBJECTIVE: To investigate tyrosine kinase inhibitors (TKI) and gold nanorods (AuNRs) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma (RCC) mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urological cancers. Likewise, the use of nanoparticles in photothermal tumour ablation, although early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNRs and activated with photothermal ablation have shown significant synergistic cell kill greater than each individual arm alone...
July 19, 2016: BJU International
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