Menée sur des lignées cellulaires établies à partir d'un épanchement pleural de cancer métastatique du sein, cette étude analyse la relation entre transcriptome, cistrome et épigénome dans la réponse des cellules cancéreuses aux rayonnement ionisants

Parallel Profiling of the Transcriptome, Cistrome, and Epigenome in the Cellular Response to Ionizing Radiation

Rashi-Elkeles, Sharon ; Warnatz, Hans-Jörg ; Elkon, Ran ; Kupershtein, Ana ; Chobod, Yuliya ; Paz, Arnon ; Amstislavskiy, Vyacheslav ; Sultan, Marc ; Safer, Hershel ; Nietfeld, Wilfried ; Lehrach, Hans ; Shamir, Ron ; Yaspo, Marie-Laure ; Shiloh, Yosef

The DNA damage response (DDR) is a vast signaling network that is robustly activated by DNA double-strand breaks, the critical lesion induced by ionizing radiation (IR). Although much of this response operates at the protein level, a critical component of the network sustains many DDR branches by modulating the cellular transcriptome. Using deep sequencing, we delineated three layers in the transcriptional response to IR in human breast cancer cells: changes in the expression of genes encoding [...]

A partir d'une revue systématique de la littérature publiée entre 1990 et 2012 (45 articles, 1047 patients), cette étude compare, du point de vue du contrôle local de la maladie et de la survie globale, l'efficacité d'une surrénalectomie, d'une radiothérapie corporelle ablative stéréotaxique et d'une ablation percutanée par cathéter dans le traitement d'oligométastases surrénales

Surgical and ablative therapies for the management of adrenal ‘oligometastases’ – A systematic review

Gunjur, Ashray ; Duong, Cuong ; Ball, David ; Siva, Shankar

We systematically reviewed the literature on the use of surgery, stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) techniques for the treatment of adrenal metastases to develop evidence-based recommendations. A systematic review of the MEDLINE database was performed using structured search terms following PRISMA guidelines. Eligible publications were those published from 1990 to 2012, written in English, had at least five patients treated for adrenal [...]

Cet article analyse l'utilisation de la "surveillance active" et des traitements localisés chez les patients atteints d'un cancer de la prostate à faible risque de récidive

Management of low risk prostate cancer : active surveillance and focal therapy

Klotz, Laurence ; Emberton, Mark

Low-risk prostate cancer, defined as Gleason Score 6 or less with PSA <10 ng/ml, is diagnosed in about half of men undergoing screening. Approximately 30% of men diagnosed with low-risk disease harbour high-grade cancer that is unrepresented on the biopsy. Moreover, a small percentage of low-grade cancers have molecular alterations that result in progression to aggressive disease. Favourable-risk prostate cancer should be managed with close follow up. Active surveillance is appropriate for most [...]

Menée à partir des données des registres américains des cancers portant sur 7 858 patients atteints d'un cancer métastatique de la prostate de stade IV récemment diagnostiqué, cette étude évalue le bénéfice, en termes de survie, d'une prostatectomie radicale ou d'une curiethérapie définitives pour traiter la tumeur primitive

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based, propensity score analysis

Antwi, Samuel ; Everson, Todd M.

Background : This study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis. Methods : Data on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and [...]

Menée à partir de données portant sur 167 patients atteints d'un carcinome à cellules rénales, cette étude montre qu'une néphrectomie partielle laparo-endoscopique assistée par robot est, lorsqu'elle utilise un seul site d'accès, moins performante en termes de durée d'ischémie chaude, de taux de marges de résection négatives et de taux de complications chirurgicales

R-LESS Partial Nephrectomy Trifecta Outcome Is Inferior to Multiport Robotic Partial Nephrectomy: Comparative Analysis

Christos Komninos, ; Tae Young Shin, ; Patrick Tuliao, ; Young Eun Yoon, ; Kyo Chul Koo, ; Chien-Hsiang Chang, ; Sang Woon Kim, ; Ji Yong Ha, ; Woong Kyu Han, ; Koon Ho Rha

Background : Trifecta achievement in partial nephrectomy (PN) is defined as the combination of warm ischemia time ≤20min, negative surgical margins, and no surgical complications. Objective : To compare trifecta achievement between robotic, laparoendoscopic, single-site (R-LESS) PN and multiport robotic PN (RPN). Design, setting, and participants : Data from 167 patients who underwent RPN from 2006 to 2012 were retrospectively analyzed. Outcome measurements and statistical analysis : Primary [...]

Menée sur 108 patients atteints d'un carcinome rhinopharyngé, cette étude compare les caractéristiques cliniques et radiologiques des nécroses du lobe temporal liées à une radiothérapie 2D ou à une radiothérapie avec modulation d'intensité

Comparison of radiological and clinical features of temporal lobe necrosis in nasopharyngeal carcinoma patients treated with 2D radiotherapy or intensity-modulated radiotherapy

Mao, Y. P. ; Zhou, G. Q. ; Liu, L. Z. ; Guo, R. ; Sun, Y. ; Li, L. ; Lin, A. H. ; Zeng, M. S. ; Kang, T. B. ; Jia, W. H. ; Shao, J. Y. ; Mai, H. Q. ; Ma, J.

Background : To compare the imaging and clinical features of temporal lobe necrosis (TLN) in nasopharyngeal carcinoma (NPC) patients treated with two-dimensional radiotherapy (2D-RT) or those with intensity-modulated radiotherapy (IMRT). Methods : We retrospectively analysed NPC patients who underwent 2D-RT (72 patients, 128 temporal lobes) or IMRT (36 patients, 50 lobes) and developed radiation-induced, MRI-confirmed TLN. Results : White-matter lesions (WMLs), contrast-enhanced lesions, cysts [...]

Menée in vitro et in vivo, cette étude évalue l'intérêt d'oligodésoxynucléotides CpG pour augmenter l'efficacité d'une immunothérapie

CpG ODN Nanorings Induce IFNα from Plasmacytoid Dendritic Cells and Demonstrate Potent Vaccine Adjuvant Activity

Gungor, Bilgi ; Yagci, Fuat Cem ; Tincer, Gizem ; Bayyurt, Banu ; Alpdundar, Esin ; Yildiz, Soner ; Ozcan, Mine ; Gursel, Ihsan ; Gursel, Mayda

CpG oligodeoxynucleotides (ODN) are short single-stranded synthetic DNA molecules that activate the immune system and have been found to be effective for preventing and treating infectious diseases, allergies, and cancers. Structurally distinct classes of synthetic ODN expressing CpG motifs differentially activate human immune cells. K-type ODN (K-ODN), which have progressed into human clinical trials as vaccine adjuvants and immunotherapeutic agents, are strong activators of B cells and [...]

Menée à l'aide de modèles murins, cette étude suggère l'intérêt d'une stratégie combinant un vaccin thérapeutique appelé TEGVAX, induisant la production d'interféron gamma, et le nivolumab, un anticorps monoclonal anti PD-1

Preclinical evidence that PD-1 blockade cooperates with cancer vaccine TEGVAX to elicit regression of established tumors

Fu, Juan ; Malm, Ian-James ; Kadayakkara, Deepak K. ; Levitsky, Hy ; Pardoll, Drew ; Kim, Young J

Biomarker studies have shown that expression of the T cell co-regulatory ligand PD-L1 on tumor cells correlates with clinical responsiveness to the PD-1 antibody nivolumab. Here we report the findings of a preclinical cancer vaccine study demonstrating a similiar correlate where PD-L1 is upregulated in the tumor microenvironment. We formulated an IFNγ-inducing cancer vaccine called TEGVAX that combined GM-CSF and multiple toll-like receptor agonists to increase the number of activated dendritic [...]

Cet article passe en revue les perspectives offertes par les nanotechnologies pour acheminer des molécules thérapeutiques à l'intérieur des tumeurs, ainsi que pour moduler le micro-environnement tumoral et améliorer l'efficacité des chimiothérapies

Drug delivery: Beyond active tumour targeting

Sagnella, Sharon M. ; McCarroll, Joshua A. ; Kavallaris, Maria

Despite improvements in our understanding of cancer and the concept of personalized medicine, cancer is still a major cause of death. It is established that solid tumours are highly heterogeneous, with a complex tumour microenvironment. Indeed, the tumour microenvironment is made up of a collection of immune cells, cancer-activated fibroblasts, and endothelial cells and in some cases a dense extracellular matrix. Accumulating evidence shows that the tumour microenvironment is a major barrier [...]

Menée sur des lignées cellulaires et à l'aide de modèles murins, cette étude évalue l'activitié antitumorale et la neurotoxicité d'un virus oncolytique élaboré à partir du virus de la stomatite vésiculaire

Re-engineering vesicular stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity and enhance oncolytic potency

Muik, Alexander ; Stubbert, Lawton J ; Jahedi, Roza Z ; Geiß, Yvonne ; Kimpel, Janine ; Dold, Catherine ; Tober, Reinhard ; Volk, Andreas ; Klein, Sabine ; Dietrich, Ursula ; Yadollahi, Beta ; Falls, Theresa ; Miletic, Hrvoje ; Stojdl, David ; Bell, John C. ; von Laer, Dorothee

As cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we have engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. The envelope glycoprotein (G) of VSV was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (LCMV-GP) creating a replicating therapeutic, rVSV(GP), that is benign in normal brain but [...]

Menée sur 51 lignées cellulaires de mélanome, notamment des lignées résistantes aux inhibiteurs de BRAF, cette étude analyse les effets de divers inhibiteurs de BRAF, MEK et PI3K sur l'expression de PD-L1

Effects of MAPK and PI3K Pathways on PD-L1 Expression in Melanoma

Atefi, Mohammad S. ; Avramis, Earl ; Lassen, Amanda ; Wong, Deborah J.L. ; Robert, Lidia ; Foulad, David ; Cerniglia, Michael ; Titz, Bjoern R ; Chodon, Thinle ; Graeber, Thomas ; Comin-Anduix, Begona ; Ribas, Antoni

Purpose: PD-L1 is the main ligand for the immune inhibitory receptor PD-1. This ligand is frequently expressed by melanoma cells. In this study we investigated whether PD-L1 expression is controlled by melanoma driver mutations and modified by oncogenic signaling inhibition. Experimental Design: Expression of PD-L1 was investigated in a panel of 51 melanoma cell lines containing different oncogenic mutations, including cell lines with innate and acquired resistance to BRAF inhibitors. The [...]

Menée in vitro et in vivo sur des modèles de carcinome séreux de l'ovaire, cette étude évalue l'activité antitumorale d'un traitement visant à inhiber l'expression du micro-ARN miR-182

Anti-MiR-182 reduces ovarian cancer burden, invasion and metastasis: An in vivo study in orthotopic xenografts of nude mice

Xu, Xiaofei ; Ayub, Bushra ; Liu, Zhaojian ; Serna, Vanida Ann ; Qiang, Wenan ; Liu, Yugang ; Hernando, Eva ; Zabludoff, Sonya ; Kurita, Takeshi ; Kong, Beihua ; Wei, Jian-Jun

High-grade serous ovarian carcinoma (HGSOC) is a fatal disease, and its grave outcome is largely due to widespread metastasis at the time of diagnosis. Current chemotherapies reduce tumor burden, but they do not provide long term benefits for cancer patients. The aggressive tumor growth and metastatic behavior characteristic of these tumors demand novel treatment options such as anti-microRNA treatment which is emerging as a potential modality for cancer therapy. MicroRNA-182 (miR-182) [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de cancer du sein, cette étude analyse l'activité anti-métastatique d'un composé appelé EW-197, un inhibiteur de ALK5

EW-7197, A Novel ALK-5 Kinase Inhibitor, Potently Inhibits Breast to Lung Metastasis

Son, Ji Yeon ; Park, So-Yeon ; Kim, Sol-Ji ; Lee, Seon Joo ; Park, Sang-A ; Kim, Min-Jin ; Kim, Seung Won ; Kim, Dae-Kee ; Nam, Jeong-Seok ; Sheen, Yhun Yhong

Advanced tumors produce an excessive amount of transforming growth factor-beta (TGF-beta), which promotes tumor progression at late stages of malignancy. The purpose of this study was to develop anti-TGF-beta therapeutics for cancer. We synthesized a novel small molecule TGF-beta receptor I kinase (ALK5) inhibitor termed N-[[4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl]-2-fluoroaniline (EW-7197), and we investigated its potential anti-metastatic [...]

Mené sur 33 patients atteints d'une tumeur solide ou d'un lymphome de stade avancé, cet essai de phase I évalue la toxicité et la dose maximale tolérée d'un composé appelé VTX-2337, un agoniste de TLR8

A Phase 1 Dose-Finding Study of the Novel Toll-like Receptor 8 Agonist VTX 2337 in Adult Subjects with Advanced Solid Tumors or Lymphoma

Hershberg, Robert M. ; Manjarrez, Kristi L ; Randall, Tressa D. ; Dietsch, Gregory N ; Northfelt, Donald W. ; Ramanathan, Ramesh K ; Cohen, Peter A ; Weiss, Glen J ; Von Hoff, Daniel D.

Purpose: This Phase 1, open-label, uncontrolled, ascending-dose study explored the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacology of the TLR8 agonist VTX-2337 in subjects with advanced solid tumors or lymphoma. Experimental Design: VTX-2337 doses (0.1-3.9 mg/m2) were administered subcutaneously on Days 1, 8, and 15 of each 28-day cycle. Safety/tolerability assessments included adverse events (AEs); physical, ophthalmologic, and laboratory evaluations; and [...]

Mené sur 152 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë, cet essai taïwanais évalue l'intérêt de retarder l'administration d'une thérapie intrathécale triple, sans irradiation crânienne, jusqu'à la disparition de blastes dans le sang périphérique

Triple Intrathecal Therapy Alone With Omission of Cranial Radiation in Children With Acute Lymphoblastic Leukemia

Liu, Hsi-Che ; Yeh, Ting-Chi ; Hou, Jen-Yin ; Chen, Kuan-Hao ; Huang, Ting-Huan ; Chang, Ching-Yi ; Liang, Der-Cherng

Purpose : To eliminate the toxicities and sequelae of cranial irradiation (CrRT) and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, a prospective study of a modified CNS-directed therapy was conducted in children with acute lymphoblastic leukemia (ALL). Patients and Methods : Since June 1999, children with newly diagnosed ALL have been treated with triple intrathecal therapy (TIT) alone without CrRT. The first TIT was delayed until the disappearance of blasts [...]

Mené en Italie et Allemagne sur 49 patients atteints d'un lymphome diffus à grandes cellules B (âge : entre 60 et 80 ans), cet essai de phase II évalue l'efficacité et la toxicité de l'ajout de lénalidomide à une chimiothérapie R-CHOP21

Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial

Vitolo, Umberto ; Chiappella, Annalisa ; Franceschetti, Silvia ; Carella, Angelo Michele ; Baldi, Ileana ; Inghirami, Giorgio ; Spina, Michele ; Pavone, Vincenzo ; Ladetto, Marco ; Liberati, Anna Marina ; Molinari, Anna Lia ; Zinzani, Pierluigi ; Salvi, Flavia ; Fattori, Pier Paolo ; Zaccaria, Alfonso ; Dreyling, Martin ; Botto, Barbara ; Castellino, Alessia ; Congiu, Angela ; Gaudiano, Marcello ; Zanni, Manuela ; Ciccone, Giovannino ; Gaidano, Gianluca ; Rossi, Giuseppe

Background : Up to 40% of elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) given a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP21) relapse or develop refractory disease. Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas. In phase 2 of the REAL07 trial, we aimed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated [...]

Mené en deux étapes sur 124 et 154 patients atteints d'un lymphome folliculaire, cet essai de phase IB compare la toxicité et des paramètres pharmacocinétiques du rituximab, par voie intraveineuse et sous-cutanée, en traitement d'entretien

Comparison of Subcutaneous Versus Intravenous Administration of Rituximab As Maintenance Treatment for Follicular Lymphoma: Results From a Two-Stage, Phase IB Study

Salar, Antonio ; Avivi, Irit ; Bittner, Beate ; Bouabdallah, Reda ; Brewster, Mike ; Catalani, Olivier ; Follows, George ; Haynes, Andrew ; Hourcade-Potelleret, Florence ; Janikova, Andrea ; Larouche, Jean-François ; McIntyre, Christine ; Pedersen, Michael ; Pereira, Juliana ; Sayyed, Pakeeza ; Shpilberg, Ofer ; Tumyan, Gayane

Purpose : This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma. Patients and Methods : In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m2, 625 mg/m2, or an additional group at 800 mg/m2) or IV rituximab (375 mg/m2). The objective was to determine an SC dose that would yield a [...]

Cet article passe en revue les travaux récents sur le traitement des métastases osseuses chez les patients atteints d'un cancer de la prostate

Managing bone metastases and reducing skeletal related events in prostate cancer

Gartrell, Benjamin A. ; Saad, Fred

Advanced-stage prostate cancer is associated with skeletal complications related to metastatic disease and its treatment. On the one hand, metastatic disease to bone is commonly associated with skeletal-related events (SREs); on the other hand, treatment with androgen-deprivation therapy (ADT) leads to loss in bone mineral density (BMD) and increased risk of fracture. Despite osteoblastic appearance on radiography, bone metastases from prostate cancer are associated with increased osteoblast [...]

Menée sur une patiente atteinte d'un cholangiocarcinome métastatique, cette étude évalue l'activité antitumorale d'une immunothérapie adoptive à base de lymphocytes T CD4+ reconnaissant une mutation du gène ERBB2IP

Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer

Tran, Eric ; Turcotte, Simon ; Gros, Alena ; Robbins, Paul F. ; Lu, Yong-Chen ; Dudley, Mark E. ; Wunderlich, John R. ; Somerville, Robert P. ; Hogan, Katherine ; Hinrichs, Christian S. ; Parkhurst, Maria R. ; Yang, James C. ; Rosenberg, Steven A.

Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved [...]

Mené sur 188 patients atteints d'un cancer du poumon non à petites cellules de stade localement avancé, inopérable et associé à un pronostic défavorable, cet essai de phase III évalue, du point de vue de la survie, de la qualité de vie et en fonction de la taille de la tumeur, l'intérêt d'une chimioradiothérapie palliative

Poor Prognosis Patients with Inoperable Locally Advanced NSCLC and Large Tumors Benefit from Palliative Chemoradiotherapy: A Subset Analysis from a Randomized Clinical Phase III Trial

Strøm, Hans H. ; Bremnes, Roy M. ; Sundstrøm, Stein H. ; Helbekkmo, Nina ; Aasebø, Ulf

Introduction: Poor prognosis patients with bulky stage III locally advanced non-small-cell lung cancer may not be offered concurrent chemoradiotherapy (CRT). Following a phase III trial concerning the effect of palliative CRT in inoperable poor prognosis patients, this analysis was performed to explore how tumor size influenced survival and health-related quality of life (HRQOL). Methods : A total of 188 poor prognosis patients recruited in a randomized clinical trial received four courses [...]

Menée sur un modèle murin d'adénocarcinome de la prostate, cette étude met en évidence l'intérêt d'une radiothérapie de l'ensemble du corps pour améliorer, dans le cadre d'une immunothérapie adoptive, la persistance et l'amplification des cellules T CD8+ transférées

Whole body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer

Ward-Kavanagh, Lindsay K ; Zhu, Junjia ; Cooper, Timothy K ; Schell, Todd D

Adoptive immunotherapy has demonstrated efficacy in a subset of clinical and preclinical studies, but the T cells used for therapy are often rapidly rendered non-functional in tumor-bearing hosts. Recent evidence indicates that prostate cancer can be susceptible to immunotherapy, but most studies using autochthonous tumor models demonstrate only short-lived T cell responses in the tolerogenic prostate microenvironment. Here, we assessed the efficacy of sublethal whole body irradiation (WBI) to [...]

A partir d'une revue de la littérature publiée entre 1976 et 2013 (278 articles), cette étude analyse les caractéristiques des tumeurs neuroendocrines de la prostate et identifie les stratégies thérapeutiques utilisées

Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review

Sargos, P. ; Ferretti, L. ; Gross-Goupil, M. ; Orre, M. ; Cornelis, F. ; Henriques de Figueiredo, B. ; Houede, N. ; Merino, C. ; Roubaud, G. ; Dallaudiere, B. ; Richaud, P. ; Flechon, A.

Objectives : Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of [...]

Cet article fait le point sur l'évaluation et la prise en charge thérapeutique des patients atteints d'un cancer de la prostate et âgés de 70 ans ou plus

Challenges of managing elderly men with prostate cancer

Jha, Gautam G. ; Anand, Vidhu ; Soubra, Ayman ; Konety, Badrinath R.

The incidence of prostate cancer increases with age. Current evidence suggests that prostate cancer is under treated in patients aged [ge]70 years, despite evidence of efficacy and acceptable toxicity. Radical cystectomy and definitive radiotherapy are often denied owing to fears of post-operative complications and radiotherapy-associated gastrointestinal and genitourinary toxicity. However, modern radical prostatectomy techniques provide excellent clinical outcomes with low perioperative [...]