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Targeted Oncology

Yu Jin Lim, Jaemoon Koh, Kyubo Kim, Eui Kyu Chie, Sehui Kim, Kyoung Bun Lee, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh, Yung-Jue Bang
BACKGROUND: There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma. OBJECTIVE: This study evaluated the clinical implications of cytotoxic T lymphocyte antigen-4 (CTLA-4) expression levels and CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in extrahepatic bile duct (EHBD) cancer. PATIENTS AND METHODS: Immunohistochemistry of CTLA-4, CD4, and CD8 was performed for 77 EHBD cancer patients undergoing surgery plus adjuvant chemoradiotherapy...
January 13, 2017: Targeted Oncology
Mario Scartozzi, Loic Vincent, Marielle Chiron, Stefano Cascinu
No abstract text is available yet for this article.
December 20, 2016: Targeted Oncology
Juan Martin-Liberal, Cinta Hierro, Maria Ochoa de Olza, Jordi Rodon
Clinical researchers in oncology face the difficulty of developing new drugs for treating cancer patients. This challenge nowadays extends towards new horizons since a high number of drugs are developed in each of the three paradigms: classical cytotoxics, new targeted agents, and emergent immunotherapeutic approaches. Over the last decade, there has been an unstoppable progress in this third paradigm, to the extent that in 2013 immunotherapy was granted the scientific breakthrough of the year. However, the novel mechanisms of action of these immunotherapeutic agents entail a whole new series of concepts, resulting in a number of unresolved questions to which clarification is crucial for their success: establishment of accurate preclinical models able to predict human toxicities, better selection of candidate populations, finding and validation of predictive biomarkers, definition of suitable endpoints, improvements in first-in-human study designs, proposal of more accurate radiological response criteria, management of novel immune-related toxicities and development of combinations based on a biological rationale...
December 20, 2016: Targeted Oncology
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...
December 15, 2016: Targeted Oncology
Jean-Luc Van Laethem, Hanno Riess, Jacek Jassem, Michael Haas, Uwe M Martens, Colin Weekes, Marc Peeters, Paul Ross, John Bridgewater, Bohuslav Melichar, Stefano Cascinu, Piotr Saramak, Patrick Michl, David Van Brummelen, Alberto Zaniboni, Wollf Schmiegel, Svein Dueland, Marius Giurescu, Vittorio L Garosi, Katrin Roth, Anke Schulz, Henrik Seidel, Prabhu Rajagopalan, Michael Teufel, Barrett H Childs
BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA...
December 14, 2016: Targeted Oncology
Joleen M Hubbard, Michelle R Mahoney, William S Loui, Lewis R Roberts, Thomas C Smyrk, Zoran Gatalica, Mitesh Borad, Shaji Kumar, Steven R Alberts
BACKGROUND: Angiogenesis has been a major target of novel drug development in hepatocellular carcinoma (HCC). It is hypothesized that the combination of two antiangiogenic agents, sorafenib and bevacizumab, will provide greater blockade of angiogenesis. OBJECTIVE: To determine the optimal dose, safety, and effectiveness of dual anti-angiogenic therapy with sorafenib and bevacizumab in patients with advanced HCC. PATIENTS AND METHODS: Patients with locally advanced or metastatic HCC not amenable for surgery or liver transplant were eligible...
December 9, 2016: Targeted Oncology
I Duran, J Lambea, P Maroto, J L González-Larriba, Luis Flores, S Granados-Principal, M Graupera, B Sáez, A Vivancos, O Casanovas
Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis...
November 15, 2016: Targeted Oncology
Isabel Heidegger, Axel Heidenreich, David Pfister
Prostate cancer is the most common cancer in men. In recent years, several new targeted therapeutic agents for the treatment of metastatic castration resistant prostate cancer (mCRPC) have been developed. These include androgen receptor targeting agents, new taxanes, radium-223, and immunotherapies. In this short review, we provide a summary of clinical and preclinical biomarkers for each of these new treatment strategies, also including new markers currently presented in conference papers only. Moreover, we address the role of these biomarkers in clinical routine with the aim to select best-personalized treatment strategies for patients...
October 27, 2016: Targeted Oncology
Aaron Vinik, Andrew Bottomley, Beata Korytowsky, Yung-Jue Bang, Jean-Luc Raoul, Juan W Valle, Peter Metrakos, Dieter Hörsch, Rajiv Mundayat, Arlene Reisman, Zhixiao Wang, Richard C Chao, Eric Raymond
OBJECTIVE: The objective of this analysis was to compare patient-reported outcomes and health-related quality of life (HRQoL) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive, well-differentiated pancreatic neuroendocrine tumors (NCT00428597). PATIENTS AND METHODS: Patients received sunitinib 37.5 mg (n = 86) or placebo (n = 85) on a continuous daily-dosing schedule until disease progression, unacceptable adverse events (AEs), or death...
December 2016: Targeted Oncology
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Targeted Oncology
Gillian M Keating
Afatinib (Giotrif(®), Gilotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of patients with advanced lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations, afatinib significantly prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of patients receiving first-line treatment for advanced lung adenocarcinoma with activating EGFR mutations, afatinib significantly prolonged PFS, but not OS, compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus cisplatin (LUX-Lung 6 trial)...
December 2016: Targeted Oncology
Martin Chopra
No abstract text is available yet for this article.
December 2016: Targeted Oncology
Radoslaw Kwapiszewski, Sebastian D Pawlak, Karolina Adamkiewicz
The epidermal growth factor receptor (EGFR) is one of the most important and attractive targets for specific anticancer therapies. It is a robust regulator of pathways involved in cancer pathogenesis and progression. Thus far, clinical trials have demonstrated the benefits of monoclonal antibodies and synthetic tyrosine kinase inhibitors in targeting this receptor; however, novel strategies are still being developed. This article reviews the current state of efforts in targeting the EGFR in cancer therapy. Following a brief characterization of EGFR, we will present a complete list of anti-EGFR agents that are already approved, and available in clinical practice...
December 2016: Targeted Oncology
Monica M Mita, John Nemunaitis, Juneko Grilley-Olson, Bassil El-Rayes, Tanios Bekaii-Saab, R Donald Harvey, John Marshall, Xiaoping Zhang, Vincent Strout
BACKGROUND: CEP-37250/KHK2804 is a recombinant, humanized, non-fucosylated, monoclonal antibody directed to sialic acid-containing glycoconjugates frequently found on certain tumor cell types. OBJECTIVE: The objective was to determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, potential immunogenicity, and preliminary clinical efficacy of CEP-37250/KHK2804 monotherapy in patients with advanced cancer in a first-in-human, phase 1 study...
December 2016: Targeted Oncology
Xue Li, Minghuan Li, Zhen Lian, Hui Zhu, Li Kong, Ping Wang, Jinming Yu
BACKGROUND: Cancer therapies that target the PD-1/PD-L1 pathway are in ongoing phase I/II clinical trials for several tumor types. However, the prognostic value of PD-L1 expression in breast cancer is unclear. OBJECTIVE: We assessed the prognostic role of PD-L1 expression in breast cancer. METHODS: We searched Medline/PubMed for eligible studies of the association between PD-L1 expression and patient survival in breast cancer published before 7 December 2015...
December 2016: Targeted Oncology
Juan Wang, Guixiang Tai
Hepatocellular carcinoma (HCC) is among the most frequently occurring cancers and the leading causes of cancer mortality worldwide. Identification of the signaling pathways regulating liver carcinogenesis is critical for developing novel chemoprevention and targeted therapies. C-Jun N-terminal kinase (JNK) is a member of a larger group of serine/threonine (Ser/Thr) protein kinases known as the mitogen-activated protein kinase (MAPK) family. JNK is an important signaling component that converts external stimuli into a wide range of cellular responses, including cell proliferation, differentiation, survival, migration, invasion, and apoptosis, as well as the development of inflammation, fibrosis, cancer growth, and metabolic diseases...
December 2016: Targeted Oncology
Akihito Tsuji, Yu Sunakawa, Wataru Ichikawa, Masato Nakamura, Mitsugu Kochi, Tadamichi Denda, Tatsuro Yamaguchi, Ken Shimada, Akinori Takagane, Satoshi Tani, Masahito Kotaka, Hidekazu Kuramochi, Kaoru Furushima, Junichi Koike, Yutaka Yonemura, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima
BACKGROUND: Retrospective studies have found that early tumor shrinkage (ETS) and depth of response (DpR) are associated with favorable outcomes in patients with metastatic colorectal cancer (mCRC); however, few prospective studies have evaluated ETS and DpR. PATIENTS AND METHODS: We performed a phase II study of FOLFOX plus cetuximab as first-line treatment in Japanese patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), chronological tumor shrinkage (evaluated every 8 weeks), and safety...
December 2016: Targeted Oncology
Maria Pinkerneil, Michèle J Hoffmann, Hella Kohlhof, Wolfgang A Schulz, Günter Niegisch
BACKGROUND: Targeting of class I histone deacetylases (HDACs) exerts antineoplastic actions in various cancer types by modulation of transcription, upregulation of tumor suppressors, induction of cell cycle arrest, replication stress and promotion of apoptosis. Class I HDACs are often deregulated in urothelial cancer. 4SC-202, a novel oral benzamide type HDAC inhibitor (HDACi) specific for class I HDACs HDAC1, HDAC2 and HDAC3 and the histone demethylase LSD1, shows substantial anti-tumor activity in a broad range of cancer cell lines and xenograft tumor models...
December 2016: Targeted Oncology
Cong Wang, Qin Yan, Minmin Hu, Di Qin, Zhenqing Feng
BACKGROUND: Ovarian cancer is one of the most common malignant gynecological cancers. Higher expression of AURKA has been found in immortalized human ovarian epithelial cells in previous studies, implying the relationship between AURKA and ovarian cancer pathogenesis. AIM: We investigated the effect of AURKA on angiogenesis and tumorigenesis of human ovarian cancer cells. METHODS: Firstly, the expression of AURKA in HO8910 and SKOV3 ovarian cancer cell lines was knocked down using a vector expressing a short hairpin small interfering RNA (shRNA)...
December 2016: Targeted Oncology
Weiya Z Wysham, Dario R Roque, Jianjun Han, Lu Zhang, Hui Guo, Paola A Gehrig, Chunxiao Zhou, Victoria L Bae-Jump
OBJECTIVE: Fatty acid synthase (FAS) is a key lipogenic enzyme that is highly expressed in endometrial cancer. Orlistat is a weight loss medication that has been shown to be a potent inhibitor of FAS. The goal of this study was to evaluate the anti-tumorigenic potential of orlistat in endometrial cancer cell lines. METHODS: The endometrial cancer cell lines ECC-1 and KLE were used. Cell proliferation was assessed by MTT assay after treatment with orlistat. Cell cycle progression was evaluated by Cellometer and apoptosis was assessed using the Annexin V assay...
December 2016: Targeted Oncology
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