Menée sur 160 patients atteints d'un cancer du poumon non à petites cellules de stade 1et inopérables selon l'indice de comorbidité de Charlson, cette étude évalue les résultats cliniques à moyen terme d'un traitement par cryoablation percutanée

Percutaneous Cryoablation for the Treatment of Medically Inoperable Stage I Non-Small Cell Lung Cancer

Yamauchi, Yoshikane ; Izumi, Yotaro ; Hashimoto, Kohei ; Yashiro, Hideki ; Inoue, Masanori ; Nakatsuka, Seishi ; Goto, Taichiro ; Anraku, Masaki ; Ohtsuka, Takashi ; Kohno, Mitsutomo ; Kawamura, Masafumi ; Nomori, Hiroaki

Background : To evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer. Methodology/Principal Findings : Between January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be [...]

Menée sur 13 patients atteints d'un lymphome hodgkinien médiastinal, cette étude compare l'impact dosimétrique d'une protonthérapie, d'une radiothérapie conformationnelle tridimensionnelle et d'une radiothérapie avec modulation d'intensité sur les différentes composantes du système cardiaque

Effective Dose Reduction to Cardiac Structures Using Protons Compared with 3DCRT and IMRT in Mediastinal Hodgkin Lymphoma

Hoppe, Bradford S. ; Flampouri, Stella ; Su, Zhong ; Latif, Naeem ; Dang, Nam H. ; Lynch, James ; Joyce, Michael ; Sandler, Eric ; Li, Zuofeng ; Mendenhall, Nancy P.

We investigated the dosimetric impact of proton therapy (PT) on various cardiac subunits in patients with Hodgkin lymphoma (HL). From June 2009 through December 2010, 13 patients were enrolled on an institutional review board-approved protocol for consolidative involved-node radiotherapy (INRT) for HL. Three separate treatment plans were developed prospectively by using three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT. Cardiac subunits were [...]

Mené sur 25 patients atteints d'un carcinome épidermoïde de l'œsophage (durée médiane de suivi : 48 mois), cet essai de phase II évalue, du point de vue de la réponse complète et de la survie globale à 3 ans, l'efficacité et la toxicité d'une photothérapie dynamique de sauvetage pour traiter des lésions locales après l'échec d'une chimioradiothérapie

Photodynamic therapy as salvage treatment for local failure after chemoradiotherapy in patients with esophageal squamous cell carcinoma: A phase II study

Yano, Tomonori ; Muto, Manabu ; Minashi, Keiko ; Iwasaki, Junko ; Kojima, Takashi ; Fuse, Nozomu ; Doi, Toshihiko ; Kaneko, Kazuhiro ; Ohtsu, Atsushi

Local failure at the primary site is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Salvage surgery is the only treatment option with curative intent, but it is associated with high morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of salvage photodynamic therapy (PDT) after CRT. Patients with histologically proven local failure limited to the submucosal layer, and without any metastasis after [...]

A partir d'une revue de la littérature publiée entre 1991 et 2012, cet article évalue les résultats cliniques et les complications d'une cryoablation de sauvetage pour traiter un cancer de la prostate récidivant localement après une radiothérapie primaire

Salvage Cryoablation for Locally Recurrent Prostate Cancer Following Primary Radiotherapy

Vladimir, Mouraviev ; Philippe, E. Spiess ; J. Stephen Jones

Context : The purpose of this paper is to review current salvage cryoablation (SCA) outcomes in patients with locally recurrent prostate cancer (PCa) following primary radiation therapy. Objective : The objectives of this review are (1) to analyze the eligibility criteria for careful patient selection for these salvage modalities and (2) to evaluate the oncologic results and reported complication rates for these respective modalities. Evidence acquisition : A Medline/PubMed literature search [...]

A partir d'une revue systématique de la littérature publiée jusqu'en janvier 2012 (389 articles, 28 études et 6 essais randomisés), cette étude évalue les résultats cliniques associés à différentes techniques chirurgicales pour traiter un cancer du rein localisé

Systematic Review of Oncologic Outcomes Following Surgical Management of Localised Renal Cancer

Steven, MacLennan ; Mari, Imamura ; Marie, C. Lapitan ; Muhammad Imran, Omar ; Thomas, B. L. Lam ; Ana, M. Hilvano-Cabungcal ; Pam, Royle ; Fiona, Stewart ; Graeme, MacLennan ; Sara, J. MacLennan ; Steven, E. Canfield ; Sam, McClinton ; T. R. Leyshon Griffiths ; Börje, Ljungberg ; James, N. ; x, ; Dow, ; Ucan Systematic Review Reference Group ; for the, E. A. U. Renal Cancer Guideline Panel n

Context : Renal cell carcinoma (RCC) accounts for 2–3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Objective : Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1–2N0M0). Evidence acquisition : Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to [...]

Menée sur 26 851 patients atteints d'un cancer localisé et invasif de la vessie et ayant reçu un traitement conservateur, cette étude américaine évalue l'impact du taux d'utilisation d'une radiothérapie définitive sur la survie globale des patients

Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy

Kozak, Kevin R. ; Hamidi, Maryam ; Manning, Matthew ; Moody, John S.

This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and [...]

Menée sur des lignées cellulaires de carcinome hépatocellulaire et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'une petite molécule, appelée FQI1, inhibant le facteur de transcription LSF

Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma

Grant, Trevor J. ; Bishop, Joshua A. ; Christadore, Lisa M. ; Barot, Girish ; Chin, Hang Gyeong ; Woodson, Sarah ; Kavouris, John ; Siddiq, Ayesha ; Gredler, Rachel ; Shen, Xue-Ning ; Sherman, Jennifer ; Meehan, Tracy ; Fitzgerald, Kevin ; Pradhan, Sriharsa ; Briggs, Laura A. ; Andrews, William H. ; Sarkar, Devanand ; Schaus, Scott E. ; Hansen, Ulla

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the prevalence of HCC, there is no effective, systemic treatment. The transcription factor LSF is a promising protein target for chemotherapy; it is highly expressed in HCC patient samples and cell lines, and promotes oncogenesis in rodent xenograft models of HCC. Here, we identify small molecules that effectively inhibit LSF cellular activity. The lead compound, factor quinolinone inhibitor 1 (FQI1), inhibits LSF [...]

Cet article passe en revue les perspectives offertes par le ciblage du métabolisme tumoral pour le traitement des cancers

Tumor metabolism as modulator of immune response and tumor progression

Gottfried, Eva ; Kreutz, Marina ; Mackensen, Andreas

About a century ago Otto Warburg observed that tumor cells exhibited increased glycolysis despite the presence of oxygen and stated this metabolic shift to glycolysis as the origin of cancer cell. In the meantime it has become clear, that the altered glucose metabolism is only one piece of the tumor metabolome puzzle. In addition, amino acid, lipid and adenosine metabolism are adapted to fulfill the tumors needs for energy and generation of building blocks such as lipids and nucleotides for new [...]

Cet article passe en revue les travaux récents sur le développement de petites molécules pour le traitement des cancers

Discovery of small molecule cancer drugs: Successes, challenges and opportunities

Hoelder, Swen ; Clarke, Paul A. ; Workman, Paul

The discovery and development of small molecule cancer drugs has been revolutionised over the last decade. Most notably, we have moved from a one-size-fits-all approach that emphasized cytotoxic chemotherapy to a personalised medicine strategy that focuses on the discovery and development of molecularly targeted drugs that exploit the particular genetic addictions, dependencies and vulnerabilities of cancer cells. These exploitable characteristics are increasingly being revealed by our [...]

Menée in vitro, cette étude suggère qu'un traitement inhibiteur de la voie ERK pourrait permettre de surmonter l'apparition d'une résistance à un traitement inhibiteur de la voie MEK

ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors

Hatzivassiliou, Georgia ; Liu, Bonnie ; O'Brien, Carol ; Spoerke, Jill M. ; Hoeflich, Klaus P. ; Haverty, Peter M. ; Soriano, Robert ; Forrest, William F. ; Heldens, Sherry ; Chen, Huifen ; Toy, Karen ; Ha, Connie ; Zhou, Wei ; Song, Kyung ; Friedman, Lori S ; Amler, Lukas C ; Hampton, Garret M. ; Moffat, John ; Belvin, Marcia ; Lackner, Mark R.

The RAS/RAF/MEK pathway is activated in over 30% of human cancers, most commonly via mutation in the K-ras oncogene but also via mutations in BRAF. Several allosteric MEK inhibitors, aimed at treating tumors with RAS/RAF pathway alterations, are in clinical development. However, acquired resistance to these inhibitors has been documented both in preclinical and clinical samples. To identify strategies to overcome this resistance, we have derived three independent MEK inhibitor-resistant cell [...]

Menée sur un modèle murin, cette étude suggère que l'inhibition de l'enzyme LSD1 pourrait, en combinaison avec un traitement à l'acide tout-trans-rétinoïque, être utile pour le traitement d'une forme de leucémie promyélocytaire aiguë

Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia

Schenk, Tino ; Chen, Weihsu Claire ; Gollner, Stefanie ; Howell, Louise ; Jin, Liqing ; Hebestreit, Katja ; Klein, Hans-Ulrich ; Popescu, Andreea C. ; Burnett, Alan ; Mills, Ken ; Casero, Robert A. ; Marton, Laurence ; Woster, Patrick ; Minden, Mark D. ; Dugas, Martin ; Wang, Jean C. Y. ; Dick, John E. ; Müller-Tidow, Carsten ; Petrie, Kevin ; Zelent, Arthur

Acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML), characterized by the t(15;17)-associated PML-RARA fusion, has been successfully treated with therapy utilizing all-trans-retinoic acid (ATRA) to differentiate leukemic blasts. However, among patients with non-APL AML, ATRA-based treatment has not been effective. Here we show that, through epigenetic reprogramming, inhibitors of lysine-specific demethylase 1 (LSD1, also called KDM1A), [...]

Menée sur 54 patients atteints d'un lymphome cutané à cellules T réfractaire ou récidivant, cette étude évalue l'efficacité et la toxicité de diverses doses de pralatrexate

Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL)

Horwitz, Steven M. ; Kim, Youn H. ; Foss, Francine ; Zain, Jasmine M. ; Myskowski, Patricia L. ; Lechowicz, Mary Jo ; Fisher, David C. ; Shustov, Andrei R. ; Bartlett, Nancy L. ; Delioukina, Maria L. ; Koutsoukos, Tony ; Saunders, Michael E. ; O'Connor, Owen A. ; Duvic, Madeleine

Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary [...]

Menée sur 20 patients atteints d'un mélanome métastatique, cette étude met en évidence un mécanisme de résistance au vémurafenib

Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance

Shi, Hubing ; Moriceau, Gatien ; Kong, Xiangju ; Lee, Mi-Kyung ; Lee, Hane ; Koya, Richard C. ; Ng, Charles ; Chodon, Thinle ; Scolyer, Richard A. ; Dahlman, Kimberly B. ; Sosman, Jeffrey A. ; Kefford, Richard F. ; Long, Georgina V. ; Nelson, Stanley F. ; Ribas, Antoni ; Lo, Roger S.

The development of acquired drug resistance hampers the long-term success of B-RAF inhibitor therapy for melanoma patients. Here we show V600EB-RAF copy-number gain as a mechanism of acquired B-RAF inhibitor resistance in 4 out of 20 (20%) patients treated with B-RAF inhibitor. In cell lines, V600EB-RAF overexpression and knockdown conferred B-RAF inhibitor resistance and sensitivity, respectively. In V600EB-RAF amplification-driven (versus mutant N-RAS-driven) B-RAF inhibitor resistance, [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale de nanoparticules, sur lesquelles ont été fixées le peptide OA02, pour le traitement d'un cancer de l'ovaire

"OA02" Peptide Facilitates the Precise Targeting of Paclitaxel-Loaded Micellar Nanoparticles to Ovarian Cancer In Vivo

Xiao, Kai ; Li, Yuanpei ; Lee, Joyce S. ; Gonik, Abby M. ; Dong, Tiffany ; Fung, Gabriel ; Sanchez, Eduardo ; Xing, Li ; Cheng, R. Holland ; Luo, Juntao ; Lam, Kit S.

Micellar nanoparticles (NPs) based on linear polyethylene glycol (PEG)-block-dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. The micellar NPs have been decorated with a high-affinity "OA02" peptide against alpha-3 integrin receptor to improve the tumor targeting specificity which is overexpressed on the surface of ovarian cancer cells. "Click chemistry" was used to conjugate alkyne-containing [...]

Menée sur 84 patients atteints d'un cancer métastatique du poumon non à petites cellules, cette étude analyse la présence d'une réponse immunitaire spontanée à une chimiothérapie

Analysis of spontaneous tumor-specific CD4 T cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response

Godet, Yann ; Fabre-Guillevin, Elizabeth ; Dosset, Magalie ; Lamuraglia, Michele ; Levionnois, Emeline ; Ravel, Patrice ; Benhamouda, Nadine ; Cazes, Aurelie ; Le Pimpec-Barthes, Francoise ; Gaugler, Beatrice - ; Langlade-Demoyen, Pierre ; Pivot, Xavier ; Saas, Philippe ; Maillere, Bernard ; Tartour, Eric ; Borg, Christophe ; ADOTEVI, Olivier

Purpose:To investigate the presence and impact of spontaneous telomerase-specific CD4 T cell responses in cancer patients. Experimental Design:A multi-step approach was used to design novel pan-HLA-DR-restricted peptides from telomerase. T cell clones isolated from cancer patient were used to characterize the polarization of telomerase-specific CD4 response. The presence of spontaneous CD4 T cell response against telomerase was monitored in 84 metastatic non-small cell lung cancer (NSCLC) [...]

Menée in vitro et in vivo, cette étude évalue l'intérêt d'un antagoniste du récepteur CXCR2, en combinaison avec l'oxaliplatine, pour le traitement d'un cancer colorectal

The CXCR2 antagonist, SCH-527123, demonstrates antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models

Ning, Yan ; LaBonte, Melissa J ; Zhang, Wu ; Bohanes, Pierre ; Gerger, Armin ; Yang, Dongyun ; Benhaim, Leonor ; Paez, David ; Rosenberg, David O ; Nagulapalli Venkata, Kalyan C ; Louie, Stan G ; Petasis, Nicos A ; Ladner, Robert D ; Lenz, Heinz-Josef D.

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States. Recent studies showed that interleukin-8 (IL-8) and its receptors (CXCR1 and CXCR2) are significantly upregulated in both the tumor and its microenvironment, and act as key regulators of proliferation, angiogenesis and metastasis. Our previous study demonstrated that IL-8 overexpression in CRC cells triggers the upregulation of the CXCR2-mediated proliferative pathway. The aim of this study was [...]

Menée in vitro et in vivo, cette étude analyse l'intérêt d'un traitement combinant le lapatinib et un composé appelé INK-128 dans le cancer du sein réfractaire au trastuzumab

Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy

Garcia, Celina ; Ibrahim, Yasir H ; Serra, Violeta ; Calvo, Maria Teresa ; Guzman, Marta ; Grueso, Judit ; Aura, Claudia ; Perez, Jose ; Jessen, Katti A ; Liu, Yi ; Rommel, Christian ; Tabernero, Josep ; Baselga, Jose ; Scaltriti, Maurizio

Purpose: The PI3K/Akt/mTOR pathway is an attractive target in HER2 positive breast cancer that is refractory to anti-HER2 therapy. The hypothesis is that suppression of this pathway results in sensitization to anti-HER2 agents. However, this combinatorial strategy has not been comprehensively tested in models of trastuzumab and lapatinib resistance. Experimental Design: We analyzed in vitro cell viability and induction of apoptosis in five different cell lines resistant to trastuzumab and [...]

Cette étude compare les effets de la doxorubicine, ainsi que du cisplatine, sur le microenvironnement tumoral dans des modèles tri- et bi-dimensionnels de cancer de l'endomètre

The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer

Chitcholtan, Kenny ; Sykes, Peter ; Evans, John

BACKGROUND:Advanced endometrial cancer often shows resistance to clinical chemotherapy although potencies of anticancer drugs in vitro are promising. The disparity suggests that in vivo microenvironments are not recapitulated by in vitro models used for preclinical testing. However, spheroids replicate some important properties of tumours in vivo. Therefore, for the first time, we compared effects of doxorubicin and cisplatin on 3D multicellular structures and 2D cell monolayers of endometrial [...]

A partir de données portant sur 373 patients présentant des métastases osseuses et ayant reçu régulièrement du denosumab pendant 3 ans, cette étude évalue différents dosages et durées du cycle d'administration du traitement

Denosumab Dose Selection for Patients with Bone Metastases from Solid Tumors

Doshi, Sameer ; Sutjandra, Liviawati ; Zheng, Jenny ; Sohn, Winnie ; Peterson, Mark ; Jang, Graham ; Chow, Andrew T ; Perez-Ruixo, Juan Jose

Purpose: Quantitatively characterize the longitudinal dose-exposure-response (urinary N-telopeptide normalized to urinary creatinine [uNTx/Cr] suppression) relationship for denosumab in patients with bone metastases from solid tumors. Experimental Design: Data from 373 patients, who received denosumab as single or multiple subcutaneous doses ranging from 30 to 180 mg (0.01 to 3 mg/kg) and administered every 4 or 12 weeks (Q4W, Q12W) for up to 3 years were used in this analysis. An inhibitory [...]

Cet article passe en revue les travaux récents ayant évalué les effets des agents stimulant l'érythropoïèse sur la progression du cancer chez les patients sous chimiothérapie

Effects of erythropoietin receptors and erythropoiesis-stimulating agents on disease progression in cancer

Aapro, M. ; Jelkmann, W. ; Constantinescu, S. N. ; Leyland-Jones, B.

Erythropoiesis-stimulating agents (ESAs) increase red blood cell (RBC) production in bone marrow by activating the erythropoietin receptor (EpoR) on erythrocytic-progenitor cells. Erythropoiesis-stimulating agents are approved in the United States and Europe for treating anaemia in cancer patients receiving chemotherapy based on randomised, placebo-controlled trials showing that ESAs reduce RBC transfusions. Erythropoiesis-stimulating agent-safety issues include thromboembolic events and [...]

Menée sur 99 patientes atteintes d'un lymphome de Hodgkin, cette étude rétrospective évalue l'impact de différentes approches thérapeutiques, combinant ou non une radiothérapie avec une chimiothérapie, sur l'issue de la grossesse démarrée après les traitements

Impact of Different Treatment Approaches on Pregnancy Outcomes in 99 Women Treated for Hodgkin Lymphoma

De Sanctis, Vitaliana ; Filippone, Francesco Romeo ; Alfò, Marco ; Muni, Roberta ; Cavalieri, Elena ; Pulsoni, Alessandro ; Annechini, Giorgia ; Valeriani, Maurizio ; Osti, Mattia Falchetto ; Minniti, Giuseppe ; Enrici, Riccardo Maurizi

The aim of this study was to evaluate the pregnancy outcomes in women with Hodgkin lymphoma (HL) diagnosis, treated between 1972 and 1999 at Department of Radiotherapy and Hematology of University “Sapienza” of Roma. We retrospectively studied 99 female patients that conceived after treatment for HL. Fifty-nine (59%) were treated with chemotherapy and radiotherapy, 32 (32%) with radiotherapy alone as supradiaphragmatic or as infradiaphragmatic and 8 (8%) patients with chemotherapy alone. [...]

Menée sur 36 patients atteints d'un cancer localisé de la prostate (durée médiane de suivi : 76, 79 ou 98 mois selon les groupes), cette étude évalue l'efficacité et la toxicité d'un traitement combinant une radiothérapie externe avec un vaccin à base de poxvirus et d'interleukine 2

Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy

Kamrava, M. ; Kesarwala, A. H. ; Madan, R. A. ; Lita, E. ; Kaushal, A. ; Tsang, K. Y. ; Poole, D. J. ; Steinberg, S. M. ; Ferrara, T. ; Dahut, W. ; Schlom, J. ; Gulley, J. L.

Background : Vaccine therapy in combination with radiation therapy may improve distant and/or local control in prostate cancer. We present long-term follow-up data on the secondary and exploratory endpoints of safety and biochemical failure, respectively, from patients with clinically localized prostate cancer treated definitively with a poxviral vector-based therapeutic vaccine combined with external beam radiation therapy (EBRT). Methods : Thirty-six prostate cancer patients received [...]

Menée sur 1 900 patients atteints d'un cancer de la prostate traité par prostatectomie (durée médiane de suivi : 5,4 ans), cette étude rétrospective montre qu'une radiothérapie de sauvetage combinée à un traitement anti-androgénique concomitant peut améliorer les résultats biochimiques chez les patients dont le niveau urinaire de l'antigène prostatique spécifique augmente après l'intervention chirurgicale

Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

Jang, Joanne W. ; Hwang, Wei-Ting ; Guzzo, Thomas J. ; Wein, Alan J. ; Haas, Naomi B. ; Both, Stefan ; Vapiwala, Neha

The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. We retrospectively reviewed the medical records from more than 1,900 post-prostatectomy patients who [...]

Menée sur des lignées cellulaires de méduloblastome et à l'aide d'échantillons tumoraux, cette étude montre que l'inhibition de l'enzyme "Polo-like kinase 1" supprime la croissance tumorale et augmente la sensibilité des cellules cancéreuses aux rayonnements ionisants

Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells

Harris, Peter ; Venkataraman, Sujatha ; Alimova, Irina ; Birks, Diane ; Donson, Andrew ; Knipstein, Jeffrey ; Dubuc, Adrian ; Taylor, Michael ; Handler, Michael ; Foreman, Nicholas ; Vibhakar, Rajeev

BACKGROUND : Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. METHODS : We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray [...]

Cet article analyse les diverses significations associées au critère de survie globale dans les essais cliniques

Overall Survival: Patient Outcome, Therapeutic Objective, Clinical Trial End Point, or Public Health Measure?

Saad, Everardo D. ; Buyse, Marc

Menée sur 687 patients inclus dans 36 essais cliniques de phase I ayant évalué une thérapie ciblée, cette étude analyse le degré de sévérité des effets indésirables associés aux traitements

Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience

Molife, L. R. ; Alam, S. ; Olmos, D. ; Puglisi, M. ; Shah, K. ; Fehrmann, R. ; Trani, L. ; Tjokrowidjaja, A. ; de Bono, J. S. ; Banerji, U. ; Kaye, S. B.

Background: This study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA).Patients and methods: A retrospective analysis of toxicity data from patients treated in phase I trials of MTAs was carried out to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk factors associated with grade 3 or more toxicity.Results: Data from 687 patients [median age, 59.1 years (range 12.5–85.5)] treated in 36 trials were analysed. Two hundred and [...]

Cet article passe en revue les modèles mathématiques permettant de choisir les critères de jugement les plus adaptés dans les essais cliniques de phase II

Choosing Phase II Endpoints and Designs: Evaluating the possibilities

LeBlanc, Michael L. ; Tangen, Catherine M.

Selecting the Phase II design and endpoint to achieve the best possible chance of success for a confirmatory Phase III study in a particular disease and treatment setting is challenging but critical. Simulating from existing clinical trial data sets, and mathematical models, can be useful tools for evaluating statistical properties.

Cet article présente une méthode qui, à base de séquençage et de screening à haut débit, vise à accélérer le processus de découverte de nouveaux médicaments anticancéreux

Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery

Li, Hairi ; Zhou, Hongyan ; Wang, Dong ; Qiu, Jinsong ; Zhou, Yu ; Li, Xiangqiang ; Rosenfeld, Michael G. ; Ding, Sheng ; Fu, Xiang-Dong

The advent of powerful genomics technologies has uncovered many fundamental aspects of biology, including the mechanisms of cancer; however, it has not been appropriately matched by the development of global approaches to discover new medicines against human diseases. Here we describe a unique high-throughput screening strategy by high-throughput sequencing, referred to as HTS2, to meet this challenge. This technology enables large-scale and quantitative analysis of gene matrices associated [...]