Menée sur des lignées de carcinome hépatocellulaire, cette étude française évalue les effets d'un inhibiteur de la polymérase PARP, la molécule ABT-888, sur la sensibilité des cellules tumorales aux rayonnements ionisants

PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitro hepatocellular carcinoma models

Guillot, Clement ; Favaudon, Vincent ; Herceg, Zdenko ; Sagne, Charlotte ; Sauvaigo, Sylvie ; Merle, Philippe ; Hall, Janet ; Chemin, Isabelle

Background : Hepatocellular carcinoma is the third cause of cancer related death for which new treatment strategies are needed. Targeting DNA repair pathways to sensitize tumor cells to chemo- or radiotherapy is under investigation for the treatment of several cancers with poly(ADP-ribose) polymerase (PARP) inhibitors showing great potential. The aim of this preclinical study was to evaluate the expression of PARP and PARG genes in a panel of liver cancer cell lines and primary human [...]

Menée sur 82 patients présentant 1 à 3 oligométastases inopérables d'origine colorectale au niveau du foie ou du poumon (durée médiane de suivi : 24 mois), cette étude évalue l'efficacité, du point de vue du contrôle local, de la survie sans progression et de la survie globale, et la toxicité d'une radiothérapie stéréotaxique ablative

Stereotactive Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach

Comito, Tiziana ; Cozzi, Luca ; Clerici, Elena ; Campisi, Maria ; Liardo, Rocco ; Navarria, Pierina ; Ascolese, AnnaMaria ; Tozzi, Angelo ; Iftode, Cristina ; De Rose, Fiorenza ; Villa, Elisa ; Personeni, Nicola ; Rimassa, Lorenza ; Santoro, Armando ; Fogliata, Antonella ; Mancosu, Pietro ; Tomatis, Stefano ; Scorsetti, Marta

Background : To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer. Methods : 82 patients with 1-3 inoperable metastases confined to one organ (liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). [...]

Menée sur 34 patients atteints d'un cancer localisé de la prostate (âge moyen : 65 ans ; durée médiane de suivi : 6 mois), cette étude évalue la sécurité et la faisabilité d'une ablation de la tumeur par électroporation irréversible

Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer

Valerio, M. ; Stricker, P. D. ; Ahmed, H. U. ; Dickinson, L. ; Ponsky, L. ; Shnier, R. ; Allen, C. ; Emberton, M.

Background : To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate. Methods : We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned [...]

Menée sur une cohorte de 2 011 patients atteints d'un cancer de la prostate traité entre 1998 et 2009 (durée médiane de suivi : 54,5 mois), cette étude évalue la toxicité urinaire à long terme d'une curiethérapie à faible débit de dose par iode 125

Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

Keyes, Mira ; Miller, Stacy ; Pickles, Tom ; Halperin, Ross ; Kwan, Winkle ; Lapointe, Vincent ; McKenzie, Michael ; Spadinger, Ingrid ; Pai, Howard ; Chan, Elisa K. ; Morris, W. James

Purpose : To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials : From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 (125I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, [...]

A partir d'une revue sytématique de la littérature publiée entre 1990 et 2014 (6 essais), cette étude évalue l'efficacité, du point de vue du contrôle biochimique, et la sécurité d'une radiothérapie hypofractionnée pour traiter un cancer de la prostate de stade précoce

A Systematic Review of Hypofractionation for Primary Management of Prostate Cancer

Bridget F. Koontz ; ; Alberto Bossi ; ; Cesare Cozzarini ; ; Thomas Wiegel ; ; Anthony D’Amico

Context : Technological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined. Objective : To perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations [...]

Mené sur 27 patients atteints d'un sarcome rétropéritonéal primitif ou récidivant traité entre 2007 et 2013 (durée médiane de suivi : 33 mois), cet essai de phase I/II évalue l'efficacité, du point de vue du contrôle local, de la survie sans progression et de la survie globale à 3 et 5 ans, et la toxicité d'une radiothérapie néoadjuvante avec modulation d'intensité et escalade de dose en combinaison avec une radiothérapie intra-opératoire

Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

Roeder, Falk ; Ulrich, Alexis ; Habl, Gregor ; Uhl, Matthias ; Saleh-Ebrahimi, Ladan ; Huber, Peter ; Schulz-Ertner, Daniela ; Nikoghosyan, Anna ; Alldinger, Ingo ; Krempien, Robert ; Mechtersheimer, Gunhild ; Hensley, Frank ; Debus, Juergen ; Bischof, Marc

Background : To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123). Methods : Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50Gy to PTV and 50-56Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12Gy). Primary endpoint was 5-year-LC, [...]

Menée sur 319 patients adultes atteints d'un sarcome primitif non métastatique des tissus mous des extrémités et traités entre 1996 et 2010 (durée médiane de suivi : 58 mois), cette étude compare, du point de vue de la récidive locale, l'efficacité d'une radiothérapie avec modulation d'intensité et d'une radiothérapie conventionnelle

Comparison of Local Recurrence With Conventional and Intensity-Modulated Radiation Therapy for Primary Soft-Tissue Sarcomas of the Extremity

Folkert, Michael R. ; Singer, Samuel ; Brennan, Murray F. ; Kuk, Deborah ; Qin, Li-Xuan ; Kobayashi, Wendy K. ; Crago, Aimee M. ; Alektiar, Kaled M.

Purpose : The use of intensity-modulated radiation therapy (IMRT) in the treatment of soft tissue sarcoma (STS) of the extremity is increasing, but no large-scale direct comparison has been reported between conventional external-beam radiation therapy (EBRT) and IMRT. Methods : Between January 1996 and December 2010, 319 consecutive adult patients with primary nonmetastatic extremity STS were treated with limb-sparing surgery and adjuvant radiotherapy (RT) at a single institution. Conventional [...]

Cet article passe en revue les perspectives offertes par le développement de traitements à base de cellules souches pour les patients atteints de cancer

Stem cell-based therapies for cancer treatment: separating hope from hype

Stuckey, Daniel W. ; Shah, Khalid

Stem cell-based therapies are emerging as a promising strategy to tackle cancer. Multiple stem cell types have been shown to exhibit inherent tropism towards tumours. Moreover, when engineered to express therapeutic agents, these pathotropic delivery vehicles can effectively target sites of malignancy. This perspective considers the current status of stem cell-based treatments for cancer and provides a rationale for translating the most promising preclinical studies into the clinic.

Cet article passe en revue les perspectives offertes par les connaissances sur les enzymes du système ubiquitine-protéasome pour le développement de thérapies ciblées dans divers cancers

Emerging Potential of Therapeutic Targeting of Ubiquitin-Specific Proteases in the Treatment of Cancer

Pal, Anupama ; Young, Matthew A. ; Donato, Nicholas J.

The ubiquitin–proteasome system (UPS) has emerged as a therapeutic focus and target for the treatment of cancer. The most clinically successful UPS-active agents (bortezomib and lenalidomide) are limited in application to hematologic malignancies, with only marginal efficacy in solid tumors. Inhibition of specific ubiquitin E3 ligases has also emerged as a valid therapeutic strategy, and many targets are currently being investigated. Another emerging and promising approach in regulation of the [...]

Menée in vitro, cette étude décrit une nouvelle classe d'inhibiteurs qui, en perturbant la conformation de la protéine Aurora A, induit la dégradation de la protéine MYCN, une protéine impliquée dans le développement de divers cancers

Drugging MYCN through an Allosteric Transition in Aurora Kinase A

Gustafson, William Clay ; Meyerowitz, Justin Gabriel ; Nekritz, Erin A ; Chen, Justin ; Benes, Cyril ; Charron, Elise ; Simonds, Erin F ; Seeger, Robert ; Matthay, Katherine K ; Hertz, Nicholas T ; Eilers, Martin ; Shokat, Kevan M ; Weiss, William A

MYC proteins are major drivers of cancer yet are considered undruggable because their DNA binding domains are composed of two extended alpha helices with no apparent surfaces for small-molecule binding. Proteolytic degradation of MYCN protein is regulated in part by a kinase-independent function of Aurora A. We describe a class of inhibitors that disrupts the native conformation of Aurora A and drives the degradation of MYCN protein across MYCN-driven cancers. Comparison of cocrystal structures [...]

Cet article passe en revue les perspectives thérapeutiques offertes par les travaux récents sur le rôle des cellules NK infiltrant les tumeurs (TINK) ou associées aux tumeurs (TANK) dans la progression et l'angiogenèse tumorales

A Think Tank of TINK/TANKs: Tumor-Infiltrating/Tumor-Associated Natural Killer Cells in Tumor Progression and Angiogenesis

Bruno, Antonino ; Ferlazzo, Guido ; Albini, Adriana ; Noonan, Douglas M.

Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This “polarization” has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as “TINKs”) [...]

Menée sur des lignées cellulaires et à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels, indépendamment de l'apparition d'une mutation secondaire dans BCR-ABL, la surexpression de la protéine kinase PRKCH dans les cellules souches de leucémie myéloïde chronique favorise une résistance à l'imatinib

A therapeutically targetable mechanism of BCR-ABL–independent imatinib resistance in chronic myeloid leukemia

Ma, Leyuan ; Shan, Yi ; Bai, Robert ; Xue, Liting ; Eide, Christopher A. ; Ou, Jianhong ; Zhu, Lihua J. ; Hutchinson, Lloyd ; Cerny, Jan ; Khoury, Hanna Jean ; Sheng, Zhi ; Druker, Brian J. ; Li, Shaoguang ; Green, Michael R.

Resistance to the BCR-ABL inhibitor imatinib mesylate (IM) poses a major problem for the treatment of chronic myeloid leukemia (CML). IM resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, in many instances, there is no mutation in BCR-ABL, and the basis of such BCR-ABL–independent IM resistance remains to be elucidated. To gain insight into BCR-ABL–independent IM resistance mechanisms, we performed a large-scale RNA interference screen and [...]

Cet article passe en revue les développements thérapeutiques récents pour les patients atteints d'un mélanome avec mutation du gène NRAS ou sans mutation des gènes BRAF et NRAS

Beyond BRAF: where next for melanoma therapy?

Fedorenko, I. V. ; Gibney, G. T. ; Sondak, V. K. ; Smalley, K. S. M.

In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases-even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the [...]

Menée in vitro, in vivo et à partir d'échantillons tumoraux prélevés sur des patients atteints d'un cancer du poumon ayant progressé après un traitement par crizotinib, cette étude suggère l'intérêt de développer des thérapies ciblées sur la signalisation IGF-1R pour surmonter la résistance thérapeutique

Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer

Lovly, Christine M. ; McDonald, Nerina T. ; Chen, Heidi ; Ortiz-Cuaran, Sandra ; Heukamp, Lukas C. ; Yan, Yingjun ; Florin, Alexandra ; Ozretic, Luka ; Lim, Diana ; Wang, Lu ; Chen, Zhao ; Chen, Xi ; Lu, Pengcheng ; Paik, Paul K. ; Shen, Ronglai ; Jin, Hailing ; Buettner, Reinhard ; Ansen, Sascha ; Perner, Sven ; Brockmann, Michael ; Bos, Marc ; Wolf, Jürgen ; Gardizi, Masyar ; Wright, Gavin M. ; Solomon, Benjamin ; Russell, Prudence A. ; Rogers, Toni-Maree ; Suehara, Yoshiyuki ; Red-Brewer, Monica ; Tieu, Rudy ; de Stanchina, Elisa ; Wang, Qingguo ; Zhao, Zhongming ; Johnson, David H. ; Horn, Leora ; Wong, Kwok-Kin ; Thomas, Roman K. ; Ladanyi, Marc ; Pao, William

Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising from the clinical observation of a patient with ALK fusion-positive lung cancer who had an exceptional response to an insulin-like growth factor 1 receptor (IGF-1R)-specific antibody, we define a [...]

Menée sur des lignées cellulaires, des modèles murins et 34 patients atteints d'un cancer de la prostate résistant à la castration et présentant des métastases osseuses, cette étude met en évidence des mécanismes permettant de rendre compte d'une efficacité clinique d'un traitement par le dovitinib, un inhibiteur de FGFR

Prostate cancer cell–stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases

Wan, Xinhai ; Corn, Paul G. ; Yang, Jun ; Palanisamy, Nallasivam ; Starbuck, Michael W. ; Efstathiou, Eleni ; Tapia, Elsa M. Li-Ning ; Zurita, Amado J. ; Aparicio, Ana ; Ravoori, Murali K. ; Vazquez, Elba S. ; Robinson, Dan R. ; Wu, Yi-Mi ; Cao, Xuhong ; Iyer, Matthew K. ; McKeehan, Wallace ; Kundra, Vikas ; Wang, Fen ; Troncoso, Patricia ; Chinnaiyan, Arul M. ; Logothetis, Christopher J. ; Navone, Nora M.

Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially [...]

Mené sur 12 et 35 patients atteints d'un cancer avancé du poumon non à petites cellules, cet essai de phase I/II évalue la dose maximale tolérée puis l'efficacité, du point de vue de la survie sans progression, d'un traitement combinant erlotinib et dasatinib

A Phase I/II Study Combining Erlotinib and Dasatinib for Non-Small Cell Lung Cancer

Gold, Kathryn A. ; Lee, J. Jack ; Harun, Nusrat ; Tang, Ximing ; Price, Justina ; Kawedia, Jitesh D. ; Tran, Hai T. ; Erasmus, Jeremy J. ; Blumenschein, George R. ; William, William N. ; Wistuba, Ignacio I. ; Johnson, Faye M.

Background. EGFR and Src are frequently activated in non-small cell lung cancer (NSCLC). In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. We conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in NSCLC. Methods. The phase I 3+3 dose-escalation study enrolled patients with solid tumors to [...]

Mené sur 91 patients atteints d'un sarcome avancé des tissus mous, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité d'un promédicament appelé TH-302, en combinaison avec la doxorubicine, pour un traitement de première ligne

Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma

Chawla, Sant P. ; Cranmer, Lee D. ; Van Tine, Brian A. ; Reed, Damon R. ; Okuno, Scott H. ; Butrynski, James E. ; Adkins, Douglas R. ; Hendifar, Andrew E. ; Kroll, Stew ; Ganjoo, Kristen N.

Purpose : TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. Patients and Methods : In this open-label phase II study, TH-302 [...]

A partir d'une revue systématique de la littérature publiée depuis 1993 (79 études identifiées), cet article présente des recommandations pour le traitement, à base de chimiothérapies et de thérapies ciblées, des patientes atteintes d'un cancer du sein HER2- de stade avancé

Chemotherapy and Targeted Therapy for Women With Human Epidermal Growth Factor Receptor 2–Negative (or unknown) Advanced Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

Partridge, Ann H. ; Rumble, R. Bryan ; Carey, Lisa A. ; Come, Steven E. ; Davidson, Nancy E. ; Di Leo, Angelo ; Gralow, Julie ; Hortobagyi, Gabriel N. ; Moy, Beverly ; Yee, Douglas ; Brundage, Shelley B. ; Danso, Michael A. ; Wilcox, Maggie ; Smith, Ian E.

Purpose : To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)– negative (or unknown) advanced breast cancer. Methods : A systematic review of randomized evidence (including systematic reviews and meta-analyses) from 1993 through to current was completed. Outcomes of interest included survival, progression-free survival, response, quality of life, and adverse effects. Guideline recommendations were evidence based and were agreed on by the Expert [...]

Mené sur 1 144 patientes atteintes d'un cancer du sein HER2- non résécable, de stade localement avancé ou métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du ramucirumab à un traitement à base de docétaxel

Primary Results of ROSE/TRIO-12, a Randomized Placebo-Controlled Phase III Trial Evaluating the Addition of Ramucirumab to First-Line Docetaxel Chemotherapy in Metastatic Breast Cancer

Mackey, John R. ; Ramos-Vazquez, Manuel ; Lipatov, Oleg ; McCarthy, Nicole ; Krasnozhon, Dmitriy ; Semiglazov, Vladimir ; Manikhas, Alexey ; Gelmon, Karen A. ; Konecny, Gottfried E. ; Webster, Marc ; Hegg, Roberto ; Verma, Sunil ; Gorbunova, Vera ; Abi Gerges, Dany ; Thireau, Francois ; Fung, Helena ; Simms, Lorinda ; Buyse, Marc ; Ibrahim, Ayman ; Martin, Miguel

Purpose : Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, [...]

Menée à partir de données portant sur 105 patients atteints d'un carcinome épidermoïde de l'anus de stade localement avancé, cette étude évalue, du point de vue du taux de réponse clinique complète, du contrôle locorégional et de la survie globale à 3 ans, l'intérêt de la capécitabine comme alternative au fluorouracile dans le cadre d'une chimioradiothérapie

Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option

Meulendijks, D. ; Dewit, L. ; Tomasoa, N. B. ; van Tinteren, H. ; Beijnen, J. H. ; Schellens, J. H. M. ; Cats, A.

Background : Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC. Methods : One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were [...]

Menée in vitro et à l'aide d'un modèle murin de cancer de l'œsophage, cette étude évalue l'efficacité de la méso-tétra (3-morpholinométhyl-4-méthoxyphényl) chlorine pour sensibiliser les cellules tumorales aux effets d'une photothérapie dynamique

Photosensitizing effectiveness of a novel chlorin-based photosensitizer for photodynamic therapy in vitro and in vivo

Zhang, Li-Jun ; Bian, Jun ; Bao, Lei-Lei ; Chen, Hai-Fei ; Yan, Yi-Jia ; Wang, Li ; Chen, Zhi-Long

Purpose : Photodynamic therapy (PDT) is a promising noninvasive treatment, which has been approved by the US Food and Drug Administration for the treatment of localized tumors. With the aim to select an appropriate photosensitizer for tumor treatment in PDT, the antitumor effect of a novel chlorin-based photosensitizer, meso-tetra (3-morphlinomethyl-4-methoxyphenyl) chlorin (TMMC) (Fig. 1a) on two types of human malignant tumor cells in vitro and a esophageal cancer model in nude mice, was [...]

Menée in vitro et à l'aide de xénogreffes de carcinome épidermoïde humain de l'œsophage, cette étude montre qu'un inhibiteur de la survivine, la molécule YM155, peut permettre d'augmenter la radiosensibilité des cellules tumorales en supprimant le point de contrôle G2 du cycle cellulaire et en bloquant le processus de réparation de l'ADN par recombinaison homologue

Small-molecule survivin inhibitor YM155 enhances radiosensitization in esophageal squamous cell carcinoma by the abrogation of G2 checkpoint and suppression of homologous recombination repair

Qin, Qin ; Cheng, Hongyan ; Lu, Jing ; Zhan, Liangliang ; Zheng, Jianchao ; Cai, Jing ; Yang, Xi ; Xu, Liping ; Zhu, Hongcheng ; Zhang, Chi ; Liu, Jia ; Ma, Jianxin ; Zhang, Xizhi ; Dai, Shengbin ; Sun, Xinchen

Background : Survivin is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma (ESCC). Methods : Cell viability was determined by CCK8 assay. The radiosensitization effect of YM155 was evaluated by clonogenic survival and progression of tumor xenograft. Cell [...]

Mené sur 30 patients atteints d'un cancer du poumon non à petites cellules de stade localement avancé (âge médian : 79 ans ; score de Charlson avant traitement : 1), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité d'une chimiothérapie S1 en combinaison avec une radiothérapie thoracique concomitante

A phase II study of S-1 chemotherapy with concurrent thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer: The Okayama Lung Cancer Study Group Trial 0801

Aoe, Keisuke ; Takigawa, Nagio ; Hotta, Katsuyuki ; Maeda, Tadashi ; Kishino, Daizo ; Nogami, Naoyuki ; Tabata, Masahiro ; Harita, Shingo ; Okada, Toshiaki ; Kubo, Toshio ; Hosokawa, Shinobu ; Fujiwara, Keiichi ; Gemba, Kenichi ; Yasugi, Masayuki ; Kozuki, Toshiyuki ; Kato, Yuka ; Katsui, Kuniaki ; Kanazawa, Susumu ; Ueoka, Hiroshi ; Tanimoto, Mitsune ; Kiura, Katsuyuki

Background : Although thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes. Methods : In this phase II trial, 30 patients aged 76 years or older with LA-NSCLC received S-1 (80 mg/m2 on days 1–14 and 29–42) and TRT (60 Gy). The primary [...]

A partir de données 2013 du registre des essais cliniques des National Institutes of Health portant sur 1 207 essais de traitement d'un cancer hématologique, cette étude analyse leurs pratiques en matière d'inclusion et d'exclusion des patients en fonction de l'âge

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

Hamaker, Marije E. ; Stauder, Reinhard ; van Munster, Barbara C.

Introduction. Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. Methods. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III [...]

Cet article présente les données cliniques ayant servi de base à la Food and Drug Administration pour autoriser, en novembre 2013, la mise sur le marché du crizotinib pour le traitement des patients atteints d'un cancer métastatique du poumon non à petites cellules avec réarrangements ALK

FDA Approval Summary: Crizotinib for the Treatment of Metastatic Non-Small Cell Lung Cancer With Anaplastic Lymphoma Kinase Rearrangements

Kazandjian, Dickran ; Blumenthal, Gideon M. ; Chen, Huan-Yu ; He, Kun ; Patel, Mona ; Justice, Robert ; Keegan, Patricia ; Pazdur, Richard

On August 26, 2011, crizotinib received accelerated approval for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by a test approved by the U.S. Food and Drug Administration (FDA). Approval was based on two single-arm trials demonstrating objective response rates (ORRs) of 50% and 61% and median response durations of 42 and 48 weeks. On November 20, 2013, crizotinib received regular approval based on confirmation [...]