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Targeted Oncology

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https://www.readbyqxmd.com/read/28527094/circulating-tumor-dna-measurement-by-picoliter-droplet-based-digital-pcr-and-vemurafenib-plasma-concentrations-in-patients-with-advanced-braf-mutated-melanoma
#1
Fanny Garlan, Benoit Blanchet, Nora Kramkimel, Alicja Puszkiel, Jean-Louis Golmard, Gaelle Noe, Nicolas Dupin, Pierre Laurent-Puig, Michel Vidal, Valerie Taly, Audrey Thomas-Schoemann
BACKGROUND: Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. OBJECTIVE: We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. PATIENTS AND METHODS: Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study...
May 19, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28508152/detection-of-her2-amplification-in-circulating-tumor-cells-of-her2-negative-gastric-cancer-patients
#2
Yuji Mishima, Satoshi Matsusaka, Keisho Chin, Mariko Mikuniya, Sayuri Minowa, Tomoko Takayama, Harumi Shibata, Ryoko Kuniyoshi, Mariko Ogura, Yasuhito Terui, Nobuyuki Mizunuma, Kiyohiko Hatake
A key to the successful use of targeted cancer therapy is the ability to preselect patients who are likely to benefit from the treatment according to molecular markers. Assessment for predicting therapy response is mostly done using tumor biopsies. However, these might not truly represent all of the patient's malignant cells because of tumor heterogeneity and/or clonal evolution during disease progression. One potential strategy that can complement primary tumor biopsy is the analysis of circulating tumor cells (CTCs)...
May 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28504299/what-we-know-about-stage-ii-and-iii-colon-cancer-it-s-still-not-enough
#3
Alberto Puccini, Martin D Berger, Wu Zhang, Heinz-Josef Lenz
The introduction of oxaliplatin as adjuvant treatment for stage III colon cancer in 2004 has been the last practice changing progress in adjuvant treatment for patients with early colon cancer. Since then, many prognostic and predictive biomarkers have been studied, but only DNA mismatch repair status has been validated as having an important prognostic value. Accordingly, TNM and clinical-pathological patterns, such as pT4 lesions and lymph node sampling <12 nodes, are the main factors that guide physicians' choice regarding adjuvant treatment...
May 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28493025/crnde-expression-positively-correlates-with-egfr-activation-and-modulates-glioma-cell-growth
#4
Karrie Mei-Yee Kiang, Xiao-Qin Zhang, Grace Pingde Zhang, Ning Li, Stephen Yin Cheng, Ming-Wai Poon, Jenny Kan-Suen Pu, Wai-Man Lui, Gilberto Ka-Kit Leung
BACKGROUND: The long non-coding RNA CRNDE has emerged as an important regulator in carcinogenesis and cancer progression. While CRNDE has previously been found to be the most highly upregulated lncRNA in glioma, detailed information on its roles in regulating cancer cell growth remains limited. OBJECTIVE: In the present study, we aimed at exploring the functional roles and underlying mechanisms of CRNDE in glioma. METHODS: We applied microarray data analysis to determine the prognostic significance of CRNDE in glioma patients and its correlation with epidermal growth factor receptor (EGFR) activation...
May 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28488183/palbociclib-a-review-in-hr-positive-her2-negative-advanced-or-metastatic-breast-cancer
#5
REVIEW
Esther S Kim, Lesley J Scott
Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates...
May 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28478525/novel-insights-into-the-treatment-of-imatinib-resistant-gastrointestinal-stromal-tumors
#6
César Serrano, Suzanne George, Claudia Valverde, David Olivares, Alfonso García-Valverde, Cristina Suárez, Rafael Morales-Barrera, Joan Carles
Gastrointestinal stromal tumors (GIST) have emerged as a compelling clinical and biological model for the rational development of therapeutic strategies targeting critical oncogenic events over the past two decades. Oncogenic activation of KIT or PDGFRA receptor tyrosine kinases is the crucial driver for GIST tumor initiation, transformation, and cancer cell proliferation. Three tyrosine kinase inhibitors (TKIs) with KIT inhibitory activity - imatinib, sunitinib, and regorafenib - are approved to treat advanced GIST and have successfully exploited this addiction to KIT oncogenic signaling, demonstrating remarkable activity in a disease that historically had no successful systemic therapy options...
May 7, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28474278/cancer-immunotherapy-with-cytokine-induced-killer-cells
#7
Juan J Mata-Molanes, Manuel Sureda González, Belén Valenzuela Jiménez, Elena Mª Martínez Navarro, Antonio Brugarolas Masllorens
Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms. Cytotoxicity mediated by CD3+CD56+ T cells depends on the major histocompatibility antigen (MHC)-independent recognition of tumor cells and the activation of signaling pathways through the natural killer group 2 member D (NKG2D) cell-surface receptor...
May 4, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28361451/long-term-duration-of-first-line-axitinib-treatment-in-advanced-renal-cell-carcinoma
#8
Brian I Rini, Victor Gruenwald, Eric Jonasch, Mayer N Fishman, Yoshihiko Tomita, M Dror Michaelson, Jamal Tarazi, Laura Cisar, Subramanian Hariharan, Angel H Bair, Brad Rosbrook, Thomas E Hutson
OBJECTIVE: We conducted a retrospective analysis of two clinical trials in treatment-naïve patients (n = 402) with advanced renal cell carcinoma (RCC) treated with axitinib. Our objective was to compare duration of treatment (DT) and clinical outcome in patients who achieved DT >18 months (longer DT) versus ≤18 months (shorter DT). PATIENTS AND METHODS: DT, objective response rate (ORR), tumor shrinkage, and overall survival (OS) were summarized for patients with longer and shorter DT...
March 30, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28357727/a-phase-ib-study-of-the-dual-pi3k-mtor-inhibitor-dactolisib-bez235-combined-with-everolimus-in-patients-with-advanced-solid-malignancies
#9
Trisha M Wise-Draper, Ganesh Moorthy, Mohamad A Salkeni, Nagla Abdel Karim, Hala Elnakat Thomas, Carol A Mercer, M Shalaan Beg, Sue O'Gara, Olugbenga Olowokure, Hassana Fathallah, Sara C Kozma, George Thomas, Olivier Rixe, Pankaj Desai, John C Morris
BACKGROUND: The combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model. OBJECTIVE: To establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed. PATIENTS AND METHODS: BEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2...
March 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28353074/gemcitabine-in-combination-with-a-second-cytotoxic-agent-in-the-first-line-treatment-of-locally-advanced-or-metastatic-pancreatic-cancer-a-systematic-review-and-meta-analysis
#10
REVIEW
Xiu-Wei Zhang, Yu-Xiang Ma, Yang Sun, Yu-Bo Cao, Qin Li, Chong-An Xu
BACKGROUND: It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC). OBJECTIVE: The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC...
March 29, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28353073/erratum-to-ongoing-response-in-braf-v600e-mutant-melanoma-after-cessation-of-intermittent-vemurafenib-therapy-a-case-report
#11
Andrew J Dooley, Avinash Gupta, Mark R Middleton
No abstract text is available yet for this article.
March 28, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28324270/obinutuzumab-a-review-in-rituximab-refractory-or-relapsed-follicular-lymphoma
#12
REVIEW
Sohita Dhillon
Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL)...
March 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28281220/the-multifaceted-roles-of-b-cells-in-solid-tumors-emerging-treatment-opportunities
#13
Nicole J Flynn, Rajasekharan Somasundaram, Kimberly M Arnold, Jennifer Sims-Mourtada
The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a variety of solid tumors, including breast, ovarian, prostate, melanoma, and colorectal cancer. The function of B cells in solid tumors is controversial, with many studies reporting a pro-tumor effect, while other studies demonstrate a role for B cells in the anti-tumor immune response...
March 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28299600/sorafenib-a-review-in-hepatocellular-carcinoma
#14
REVIEW
Gillian M Keating
Sorafenib (Nexavar(®)) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall survival (OS) and time to radiological progression (TTP) with sorafenib 400 mg twice daily than with placebo, with no significant between-group difference in the median time to symptomatic progression (TTSP)...
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28255845/anti-pd-l1-atezolizumab-induced-autoimmune-diabetes-a-case-report-and-review-of-the-literature
#15
REVIEW
Laura Hickmott, Hugo De La Peña, Helen Turner, Fathelrahman Ahmed, Andrew Protheroe, Ashley Grossman, Avinash Gupta
Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes...
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28243959/mirnas-as-biomarkers-and-therapeutic-targets-in-non-small-cell-lung-cancer-current-perspectives
#16
Mateusz Florczuk, Adam Szpechcinski, Joanna Chorostowska-Wynimko
Lung cancer is the most common cancer worldwide. Up to 85% of lung cancer cases are diagnosed as non-small cell lung cancer (NSCLC). The effectiveness of NSCLC treatment is expected to be improved through the implementation of robust and specific biomarkers. MicroRNAs (miRNAs) are small, non-coding molecules that play a key role in the regulation of basic cellular processes, including differentiation, proliferation and apoptosis, by controlling gene expression at the post-transcriptional level. Deregulation of miRNA activity results in the loss of homeostasis and the development of a number of pathologies, including lung cancer...
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28120215/erratum-to-a-combination-of-the-telomerase-inhibitor-bibr1532-and-paclitaxel-synergistically-inhibit-cell-proliferation-in-breast-cancer-cell-lines
#17
Yi Shi, Lin Sun, Ge Chen, Dongyan Zheng, Li Li, Wanguo Wei
No abstract text is available yet for this article.
April 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#18
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28000147/erratum-to-aflibercept-a-new-way-to-target-angiogenesis-in-the-second-line-treatment-of-metastatic-colorectal-cancer-mcrc
#19
Mario Scartozzi, Loic Vincent, Marielle Chiron, Stefano Cascinu
No abstract text is available yet for this article.
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#20
Konstantina Skaltsa, Cristina Ivanescu, Shevani Naidoo, De Phung, Stefan Holmstrom, Nicholas R Latimer
BACKGROUND: If patients in oncology trials receive subsequent therapy, standard intention-to-treat (ITT) analyses may inaccurately estimate the overall survival (OS) effect of the investigational product. In this context, a post-hoc analysis of the phase 3 PREVAIL study was performed with the aim to compare enzalutamide with placebo in terms of OS, adjusting for potential confounding from switching to antineoplastic therapies that are not part of standard metastatic castration-resistant prostate cancer (mCRPC) treatment pathways in some jurisdictions...
February 2017: Targeted Oncology
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