Menée in vitro et à l'aide d'un modèle murin de gliome, cette étude montre que le jeûne peut augmenter la réponse des cellules tumorales à la chimiothérapie et à la radiothérapie

Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy

Safdie, Fernando ; Brandhorst, Sebastian ; Wei, Min ; Wang, Weijun ; Lee, Changhan ; Hwang, Saewon ; Conti, Peter S. ; Chen, Thomas C. ; Longo, Valter D.

Background : Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially [...]

Mené sur 90 patients atteints d'un cancer gastrique de stade III-IV(M0) traité par gastrectomie R0 et curage ganglionnaire D2, cet essai coréen de phase III évalue, du point de vue de la survie sans récidive et de la survie sans maladie, l'intérêt d'ajouter une radiothérapie à une chimiothérapie par fluorouracile et leucovorine

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

Kim, Tae Hyun ; Park, Sook Ryun ; Ryu, Keun Won ; Kim, Young-Woo ; Bae, Jae-Moon ; Lee, Jun Ho ; Choi, Il Ju ; Kim, Yeon-Joo ; Kim, Dae Yong

To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. Between May 6, 2002 and June 29, 2006, a total of 90 [...]

A partir des données d'un registre américain portant sur une cohorte de10 923 patients atteints d'un cancer du poumon non à petites cellules de stade précoce IA-IB (âge : 66 ans ou plus ; durée médiane de suivi : 3,2 ans), cette étude compare, du point de vue de la survie spécifique et de la survie globale, l'efficacité de 5 stratégies thérapeutiques : lobectomie, résection sub-lobaire, radiothérapie conventionnelle, radiothérapie ablative stéréotaxique et surveillance

Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

Shirvani, Shervin M. ; Jiang, Jing ; Chang, Joe Y. ; Welsh, James W. ; Gomez, Daniel R. ; Swisher, Stephen ; Buchholz, Thomas A. ; Smith, Benjamin D.

The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, [...]

Menée sur 2 290 patients atteints d'un carcinome urothélial de la vessie traité entre 1971 et 2011, cette étude évalue, du point de vue de la survie globale et de la survie sans récidive à 5 ans, l'intérêt d'une cystectomie radicale de sauvetage après l'échec d'une cystectomie partielle (durée médiane de suivi après cystectomie radicale : 10,9 ans)

Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy

Bruins, Harman M. ; Wopat, Ross ; Mitra, Anirban P. ; Cai, Jie ; Miranda, Gus ; Skinner, Eila C. ; Daneshmand, Siamak

Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Data on the oncological outcomes in patients undergoing salvage cystectomy for recurrent disease following bladder-sparing treatment is limited and mostly based on case reports. We present the clinical outcomes and prognostic factors in patients undergoing radical cystectomy for recurrent disease following partial cystectomy with long-term follow-up. OBJECTIVE * • To report the [...]

Menée sur des lignées cellulaires de cancer de la prostate, cette étude met en évidence un mécanisme par lequel les inhibiteurs d'histone déacétylase induisent une transition épithélio-mésenchymateuse

Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition in Prostate Cancer Cells

Kong, Dejuan ; Ahmad, Aamir ; Bao, Bin ; Li, Yiwei ; Banerjee, Sanjeev ; Sarkar, Fazlul H.

Clinical experience of histone deacetylase inhibitors (HDACIs) in patients with solid tumors has been disappointing; however, the molecular mechanism of treatment failure is not known. Therefore, we sought to investigate the molecular mechanism of treatment failure of HDACIs in the present study. We found that HDACIs Trichostatin A (TSA) and Suberoylanilide hydroxamic acid (SAHA) could induce epithelial-to-mesenchymal transition (EMT) phenotype in prostate cancer (PCa) cells, which was [...]

Menée à l'aide de modèles murins, cette étude évalue la faisabilité d'utiliser des nanoparticules fluorescentes pour développer des traitements photodynamiques non invasifs des cancers

In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers

Idris, Niagara Muhammad ; Gnanasammandhan, Muthu Kumara ; Zhang, Jing ; Ho, Paul C. ; Mahendran, Ratha ; Zhang, Yong

Conventional photodynamic therapy (PDT) is limited by the penetration depth of visible light needed for its activation. Here we used mesoporous-silica–coated upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert deeply penetrating near-infrared light to visible wavelengths and a carrier of photosensitizers. We also used the multicolor-emission capability of the UCNs at a single excitation wavelength for simultaneous activation of two photosensitizers for enhanced PDT. We [...]

Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel l'inhibiteur de l'activateur du plasmogène 1 régule l'apoptose dans les cellules tumorales

Protumorigenic Activity of Plasminogen Activator Inhibitor-1 Through an Antiapoptotic Function

Fang, Hua ; Placencio, Veronica R. ; DeClerck, Yves A.

Background Plasminogen activator inhibitor-1 (PAI-1) is a protease inhibitor but is paradoxically associated with poor outcomes in cancer patients. However, the mechanisms of its effects on tumor cells have not been explored.Methods Endogenous PAI-1 in human tumor cell lines (HT-1080, A549, HCT-116, and MDA-MB-231) was suppressed by small interfering RNAs (siRNAs) and PAI-039, a small molecule inhibitor of PAI-1, and the effects on apoptosis were examined. Tumorigenicity of PAI-1 knockdown (KD) [...]

Menée sur un modèle murin de mélanome avec mutations du gène NRAS, cette étude suggère l'efficacité d'un traitement basé sur l'inhibition conjointe des protéines kinases MEK et CDK4

Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma

Kwong, Lawrence N. ; Costello, James C. ; Liu, Huiyun ; Jiang, Shan ; Helms, Timothy L. ; Langsdorf, Aliete E. ; Jakubosky, David ; Genovese, Giannicola ; Muller, Florian L. ; Jeong, Joseph H. ; Bender, Ryan P. ; Chu, Gerald C. ; Flaherty, Keith T. ; Wargo, Jennifer A. ; Collins, James J. ; Chin, Lynda

The discovery of potent inhibitors of the BRAF proto-oncogene has revolutionized therapy for melanoma harboring mutations in BRAF, yet NRAS-mutant melanoma remains without an effective therapy. Because direct pharmacological inhibition of the RAS proto-oncogene has thus far been unsuccessful, we explored systems biology approaches to identify synergistic drug combination(s) that can mimic RAS inhibition. Here, leveraging an inducible mouse model of NRAS-mutant melanoma, we show that [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt d'un traitement à base d'inhibiteurs des voies Hedgehog et Notch pour surmonter une résistance au docétaxel chez les patients atteints d'un cancer de la prostate

Suppression of Acquired Docetaxel Resistance in Prostate Cancer through Depletion of Notch- and Hedgehog-Dependent Tumor-Initiating Cells

Domingo-Domenech, Josep ; Vidal, Samuel J ; Rodriguez-Bravo, Veronica ; Castillo-Martin, Mireia ; Quinn, S.  Aidan ; Rodriguez-Barrueco, Ruth ; Bonal, Dennis M ; Charytonowicz, Elizabeth ; Gladoun, Nataliya ; de la Iglesia-Vicente, Janis ; Petrylak, Daniel P ; Benson, Mitchell C ; Silva, Jose M ; Cordon-Cardo, Carlos

Acquired resistance to Docetaxel precedes fatality in hormone-refractory prostate cancer (HRPC). However, strategies that target Docetaxel resistant cells remain elusive. Using in vitro and in vivo models, we identified a subpopulation of cells that survive Docetaxel exposure. This subpopulation lacks differentiation markers and HLA class I (HLAI) antigens, while overexpressing the Notch and Hedgehog signaling pathways. These cells were found in prostate cancer tissues and were related to tumor [...]

Menée in vitro, cette étude évalue l'activité d'un analogue nucléosidique de l'adénosine, 8-NH2-Ado, dans les cellules de cancers du sein triplement négatifs

8-amino-adenosine Activates p53-Independent Cell Death of Metastatic Breast Cancers

Polotskaia, Alla ; Hoffman, Sandy ; Krett, Nancy L ; Shanmugam, Mala ; Rosen, Steven T. ; Bargonetti, Jill

8-amino-adenosine (8-NH2-Ado) is a ribose sugar nucleoside analogue that reduces cellular ATP levels and inhibits mRNA synthesis. Estrogen receptor negative (ER-), metastatic breast cancers often contain mutant p53; therefore we asked if 8-NH2-Ado could kill breast cancer cells without activating the p53-pathway. Regardless of the breast cancer sub-type tested, or the p53 status of the cells, 8-NH2-Ado was more cytotoxic than either gemcitabine or etoposide. 8-NH2-Ado treatment inhibited cell [...]

Menée sur des lignées cellulaires, cette étude suggère l'intérêt d'un composé appelé PF-5480090, un inhibiteur de la protéase ADAM-17, dans les cancers du sein triplement négatifs

ADAM-17: a novel therapeutic target for triple negative breast cancer

McGowan, P. M. ; Mullooly, M. ; Caiazza, F. ; Sukor, S. ; Madden, S. F. ; Maguire, A. A. ; Pierce, A. ; McDermott, E. W. ; Crown, J. ; O'Donovan, N. ; Duffy, M. J.

Background: Validated targeted therapy is currently unavailable for patients with invasive breast cancer negative for oestrogen receptors, progesterone receptors and HER2 [i.e., those with triple-negative (TN) disease]. ADAM-17 is a protease involved in the activations of several ligands that bind to and promotes intracellular signalling from the EGFR/HER family of receptors. Patients and methods: Expression of ADAM-17 was measured in 86 triple-negative and 96 non-triple-negative breast [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence un mécanisme par lequel une signalisation défaillante des voies de réponse aux atteintes à l'ADN induit une résistance à la chimiothérapie dans les carcinomes épidermoïdes de la cavité buccale

Deficient DNA damage signaling leads to chemoresistance to cisplatin in oral cancer

Wang, Ling ; Mosel, Adam J ; Oakley, Gregory G ; Peng, Aimin

Activation of the cellular DNA damage response (DDR) is an important determinant of cell sensitivity to cisplatin and other chemotherapeutic drugs that eliminate tumor cells through induction of DNA damage. It is therefore important to investigate whether alterations of the DNA damage signaling pathway confer chemoresistance in cancer cells, and whether pharmacological manipulation of the DDR pathway can re-sensitize these cells to cancer therapy. In a panel of oral/laryngeal squamous cell [...]

Cet article passe en revue les travaux récents sur la prise en charge des effets indésirables de nature immunitaire associés à l'ipilimumab chez les patients atteints d'un mélanome métastatique ou avancé

Characteristics and management of immune-related adverse effects associated with ipilimumab, a new immunotherapy for metastatic melanoma

Stephanie Andrews ; Rita Holden

Abstract:

Mené sur 913 patients atteints d'un cancer non épidermoïde du poumon non à petites cellules de stade avancé ou métastatique, cet essai international de phase III évalue, du point de vue de la survie globale, l'ajout d'aflibercept au docétaxel après un traitement à base de sels de platine

Aflibercept and Docetaxel Versus Docetaxel Alone After Platinum Failure in Patients With Advanced or Metastatic Non–Small-Cell Lung Cancer: A Randomized, Controlled Phase III Trial

Ramlau, Rodryg ; Gorbunova, Vera ; Ciuleanu, Tudor Eliade ; Novello, Silvia ; Ozguroglu, Mustafa ; Goksel, Tuncay ; Baldotto, Clarissa ; Bennouna, Jaafar ; Shepherd, Frances A. ; Le-Guennec, Solenn ; Rey, Augustin ; Miller, Vincent ; Thatcher, Nicholas ; Scagliotti, Giorgio

Purpose To compare the efficacy of aflibercept (ziv-aflibercept), a recombinant human fusion protein targeting the vascular endothelial growth factor (VEGF) pathway, with or without docetaxel in platinum-pretreated patients with advanced or metastatic nonsquamous non–small-cell lung cancer.Patients and Methods In this international, double-blind, placebo-controlled phase III trial, 913 patients were randomly assigned to (ziv-)aflibercept 6 mg/kg intravenous (IV; n = 456) or IV placebo (n = [...]

Mené sur 38 patients atteints d'un cancer de la prostate métastatique et résistant à la castration, cet essai suisse de phase II évalue, du point de vue de la survie sans progression, l'ajout de cetuximab au docétaxel

Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07)

Cathomas, Richard ; Rothermundt, Christian ; Klingbiel, Dirk ; Bubendorf, Lukas ; Jaggi, Rolf ; Betticher, Daniel C. ; Brauchli, Peter ; Cotting, Denise ; Droege, Cornelia ; Winterhalder, Ralph ; Siciliano, Daniele ; Berthold, Dominik R. ; Pless, Miklos ; Schiess, Ralph ; von Moos, Roger ; Gillessen, Silke

Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in the majority of metastatic castration-resistant prostate cancers (mCRPC) and might represent a valid therapeutic target. The combination of docetaxel and cetuximab, the monoclonal antibody against EGFR, has not been tested in prostate cancer patients. Experimental design: Patients with mCRPC progressing during or within 90 days after at least 12 weeks of docetaxel were included in this phase II trial. Treatment consisted [...]

Menée sur 49 patients atteints d'un carcinome épidermoïde de la tête et du cou localement avancé de stade III ou IV, cette étude évalue, du point de vue de la survie sans progression et de la survie globale à deux ans, l'efficacité et la toxicité d'un protocole thérapeutique comportant trois cycles de chimiothérapie d'induction par docétaxel-cisplatine-5-fluorouracile puis une radiothérapie concomitante combinée au cetuximab

Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced squamous cell carcinoma of the head and neck

Keil, Felix ; Selzer, Edgar ; Berghold, Andrea ; Reinisch, Sabine ; Kapp, Karin S. ; De Vries, Alexander ; Greil, Richard ; Bachtiary, Barbara ; Tinchon, Christoph ; Anderhuber, Wolfgang ; Burian, Martin ; Kasparek, Anne-Katrin ; Elsäßer, Wolfgang ; Kainz, Herbert ; Riedl, Regina ; Kopp, Michael ; Kornek, Gabriela

Purpose To determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer. Patients and methods Forty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1 and infusional [...]

Cet article passe en revue les enjeux associés au développement de thérapies ciblées dans les cancers rares

Targeted therapy in rare cancers: adopting the orphans

Munoz, Javier ; Kurzrock, Razelle

Designation of a rare 'orphan' disease is usually conferred by a prevalence of one in 1,500 to 2,500 individuals. Increasingly, orphan diseases are also being defined by their molecular fingerprints. Rare diseases are uniquely challenging from a therapeutic standpoint; it is critical to modify clinical study design of treatments for orphan disorders as well as for the increasingly smaller molecular subsets within frequently occurring cancers. In spite of the immense challenges associated with [...]

Ce rapport de l'American Association for Cancer Research présente les progrès réalisés en 2012 dans la prévention et le traitement des cancers

AACR Cancer Progress Report 2012

AACR Cancer Progress Report Writing Committee

It is a new day for cancer research and for cancer patients. Rapidly evolving technology is enabling extraordinary advances in cancer research that deepen our understanding of how cancer develops, grows and threatens the lives of millions. By exploiting this growing body of knowledge about cancer biology, we can be more strategic and innovative than ever before in the way we attack cancer. This is quickening the pace of developing new ways to prevent, detect, diagnose and treat cancer.The AACR [...]