Cet article passe en revue les découvertes récentes concernant la radiothérapie dans le traitement des cancers, puis analyse comment améliorer son efficacité en agissant sur ses mécanismes d'action et non sur la dose de rayonnements délivrée

Opportunities and challenges of radiotherapy for treating cancer

Schaue, Dorthe ; McBride, William H.

The past 20 years have seen dramatic changes in the delivery of radiation therapy, but the impact of radiobiology on the clinic has been far less substantial. A major consideration in the use of radiotherapy has been on how best to exploit differences between the tumour and host tissue characteristics, which in the past has been achieved empirically by radiation-dose fractionation. New advances are uncovering some of the mechanistic processes that underlie this success story. In this Review, we [...]

Menée à partir de données portant sur 568 patients atteints d'un cancer du poumon non à petites cellules de stade II traité entre 2004 et 2014 par chimioradiothérapie définitive (durée médiane de suivi : 12,9 mois), cette étude évalue la survie des patients en fonction de la dose de rayonnements administrée (doses ≥59 Gy)

Definitive chemotherapy and radiotherapy in patients with stage II non-small cell lung cancer: a population-based outcomes study

Sampath, Sagus ; Hall, Matthew ; Schultheiss, Timothy E.

Objectives : There is a paucity of data on non-surgical outcomes specific to stage II non-small cell lung cancer (NSCLC) patients receiving definitive chemotherapy and radiation therapy (CRT). This study reports population-based outcomes for this subgroup, and investigates a radiation dose-response for overall survival. Materials and Methods : The National Oncology Data Alliance (NODA), a merging of multiple tumor registries maintained by Elekta® medical systems, was queried for stage II [...]

Menée sur 1 100 patients atteints d'un cancer de la prostate à haut risque de récidive traité entre 2002 et 2013 (âge médian : 63 ans ; durée moyenne de suivi : 53 mois), cette étude multicentrique évalue, du point de vue de la survie sans récidive biochimique, de la survie sans récidive clinique et du taux de traitements de sauvetage, l'efficacité d'une prostatectomie radicale assistée par robot

Long-term Cancer Control Outcomes in Patients with Clinically High-risk Prostate Cancer Treated with Robot-assisted Radical Prostatectomy: Results from a Multi-institutional Study of 1100 Patients

Abdollah, Firas ; Sood, Akshay ; Sammon, Jesse D. ; Hsu, Linda ; Beyer, Burkhard ; Moschini, Marco ; Gandaglia, Giorgio ; Rogers, Craig G. ; Haese, Alexander ; Montorsi, Francesco ; Graefen, Markus ; Briganti, Alberto ; Menon, Mani

Background : Long-term cancer control outcomes in clinically high-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP) remain unknown. Objective : To report on long-term biochemical recurrence (BCR)–free survival, clinical recurrence (CR)–free survival, and salvage therapy rates in these patients. Given the heterogeneity of high-risk patients, a second objective was to stratify them according to their BCR risk (using preoperative parameters), in an effort [...]

Menée sur 952 patients atteints d'un carcinome à cellules rénales de stade I, cette étude identifie les caractéristiques clinicopathologiques des patients, puis compare, du point de vue de la survie globale à 5 ans, l'efficacité d'une néphrectomie partielle et d'une néphrectomie radicale en fonction de catégories d'âge

Comparison of survival rates in stage 1 renal cell carcinoma between partial nephrectomy and radical nephrectomy patients according to age distribution: a propensity score matching study

Takagi, Toshio ; Kondo, Tsunenori ; Iizuka, Junpei ; Omae, Kenji ; Kobayashi, Hirohito ; Yoshida, Kazuhiko ; Hashimoto, Yasunobu ; Tanabe, Kazunari

Objective : To assess differences in overall survival (OS) between patients receiving partial nephrectomy (PN) and radical nephrectomy (RN) for stage 1 renal cell carcinoma (RCC) according to age distribution, as the survival advantage of PN vs RN has been unclear owing to conflicting data. Patients and Methods : We studied 952 patients with stage 1 RCC who underwent either PN or RN. Patients were divided into three groups according to age: Group 1 (≤54 years), Group 2 (55–64 years), and Group [...]

Cet article présente les recommandations de l'"American Society for Radiation Oncology" sur l'utilisation post-opératoire de la radiothérapie dans le traitement d'un cancer de l'endomètre

Postoperative Radiation Therapy for Endometrial Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline

Meyer, Larissa A. ; Bohlke, Kari ; Powell, Matthew A. ; Fader, Amanda N. ; Franklin, Gregg E. ; Lee, Larissa J. ; Matei, Daniela ; Coallier, Lourie ; Wright, Alexi A.

Purpose : To provide guidance on the role of adjuvant radiation therapy in the treatment of endometrial cancer. Methods : “The Role of Postoperative Radiation Therapy for Endometrial Cancer: An ASTRO Evidence-Based Guideline” by Klopp et al, published in 2014 in Practical Radiation Oncology, was reviewed for developmental rigor by methodologists. The American Society for Radiation Oncology (ASTRO) guideline content and recommendations were further reviewed by the American Society of Clinical [...]

Cet article passe en revue les perspectives de développement thérapeutique offertes par les travaux récents sur les mécanismes par lesquels des populations sous-clonales coopèrent pour favoriser la progression de tumeurs hétérogènes

Tumorigenesis: it takes a village

Tabassum, Doris P. ; Polyak, Kornelia

Although it is widely accepted that most cancers exhibit some degree of intratumour heterogeneity, we are far from understanding the dynamics that operate among subpopulations within tumours. There is growing evidence that cancer cells behave as communities, and increasing attention is now being directed towards the cooperative behaviour of subclones that can influence disease progression. As expected, these interactions can add a greater layer of complexity to therapeutic interventions in [...]

Menée sur des lignées cellulaires de divers types de cancer et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en inhibant l'effet Warburg et la lipogenèse, un agoniste inverse du récepteur nucléaire LXR (SR9243) exerce une activité antitumorale n'induisant ni toxicité hépatique ni inflammation

Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis

Flaveny, Colin A ; Griffett, Kristine ; El-Gendy, Bahaa El-Dien M ; Kazantzis, Melissa ; Sengupta, Monideepa ; Amelio, Antonio L ; Chatterjee, Arindam ; Walker, John ; Solt, Laura A ; Kamenecka, Theodore M ; Burris, Thomas P

Malignant cells exhibit aerobic glycolysis (the Warburg effect) and become dependent on de novo lipogenesis, which sustains rapid proliferation and resistance to cellular stress. The nuclear receptor liver-X-receptor (LXR) directly regulates expression of key glycolytic and lipogenic genes. To disrupt these oncogenic metabolism pathways, we designed an LXR inverse agonist SR9243 that induces LXR-corepressor interaction. In cancer cells, SR9243 significantly inhibited the Warburg effect and [...]

Menée sur des lignées cellulaires, cette étude met en évidence des mécanismes suggérant l'intérêt de combiner inhibiteurs de Chk1 et de MK2 pour le traitement d'un cancer lié à l'activation de KRAS ou de BRAF

A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer

Dietlein, Felix ; Kalb, Bastian ; Jokic, Mladen ; Noll, Elisa M ; Strong, Alexander ; Tharun, Lars ; Ozretic, Luka ; Künstlinger, Helen ; Kambartel, Kato ; Randerath, Winfried J ; Jüngst, Christian ; Schmitt, Anna ; Torgovnick, Alessandro ; Richters, André ; Rauh, Daniel ; Siedek, Florian ; Persigehl, Thorsten ; Mauch, Cornelia ; Bartkova, Jirina ; Bradley, Allan ; Sprick, Martin R ; Trumpp, Andreas ; Rad, Roland ; Saur, Dieter ; Bartek, Jiri ; Wolf, Jürgen ; Büttner, Reinhard ; Thomas, Roman K ; Reinhardt, H.  Christian

KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels, en induisant les mitochondries à se redistribuer vers le cytosquelette, un inhibiteur de PI3K est paradoxalement susceptible de favoriser le processus métastatique

PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion

Caino, M. Cecilia ; Ghosh, Jagadish C. ; Chae, Young Chan ; Vaira, Valentina ; Rivadeneira, Dayana B. ; Faversani, Alice ; Rampini, Paolo ; Kossenkov, Andrew V. ; Aird, Katherine M. ; Zhang, Rugang ; Webster, Marie R. ; Weeraratna, Ashani T. ; Bosari, Silvano ; Languino, Lucia R. ; Altieri, Dario C.

Molecular therapies are hallmarks of “personalized” medicine, but how tumors adapt to these agents is not well-understood. Here we show that small-molecule inhibitors of phosphatidylinositol 3-kinase (PI3K) currently in the clinic induce global transcriptional reprogramming in tumors, with activation of growth factor receptors, (re)phosphorylation of Akt and mammalian target of rapamycin (mTOR), and increased tumor cell motility and invasion. This response involves redistribution of [...]

Menée sur des lignées cellulaires de lymphome et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'un inhibiteur d'histone désacétylase (ACY-1215), seul ou en combinaison avec du bortézomib

Dual targeting of protein degradation pathways with the selective HDAC6 inhibitor, ACY-1215, and bortezomib is synergistic in lymphoma

Amengual, Jennifer E. ; Johannet, Paul M ; Lombardo, Maximilian ; Zullo, Kelly M ; Hoehn, Daniela ; Bhagat, Govind ; Scotto, Luigi ; Jirau-Serrano, Xavier ; Radeski, Dejan ; Heinen, Jennifer ; Jiang, Hongfeng ; Cremers, Serge ; Zhang, Yuan ; Jones, Simon S. ; O'Connor, Owen A.

Purpose: Pan-class histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform selective HDAC inhibitors are emerging as potentially more targeted agents. HDAC6 is a class IIb deacetylase that facilitates misfolded protein transport to the aggresome for degradation. We investigated the mechanism and therapeutic impact of the selective HDAC6 inhibitor ACY-1215 alone and in combination with bortezomib in preclinical models of lymphoma. Experimental Design: [...]

Cet article passe en revue les travaux récents sur le développement de diverses formes d'immunothérapie pour les patients atteints d'un myélome multiple

Immunotherapy for multiple myeloma: Current status and future directions

Ayed, Ayed O. ; Chang, Lung-Ji ; Moreb, Jan S.

Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies and has been in the limelight of fast-track development of novel drugs that have contributed to the transformation of a rapidly lethal disease into a chronic illness with significant improvement in quality of life. Nonetheless, MM remains an incurable disease in many patients. Immunotherapy has been one of the approaches that had the highest hope for curing this disease. More than two [...]

Menée sur une xénogreffe de cancer de l'ovaire à l'aide de nanoparticules comportant un dispositif générateur de chaleur, cette étude met en évidence des mécanismes suggérant l'intérêt de manipuler la température du micro-environnement tumoral pour améliorer l'acheminement des agents cytotoxiques à l'intérieur des tumeurs

Endothelial thermotolerance impairs nanoparticle transport in tumors

Bagley, Alexander F ; Scherz-Shouval, Ruth ; Galie, Peter A ; Zhang, Angela Q ; Wyckoff, Jeffrey ; Whitesell, Luke ; Chen, Christopher S ; Lindquist, Susan ; Bhatia, Sangeeta N.

The delivery of diagnostic and therapeutic agents to solid tumors is limited by physical transport barriers within tumors, and such restrictions directly contribute to decreased therapeutic efficacy and the emergence of drug resistance. Nanomaterials designed to perturb the local tumor environment with precise spatiotemporal control have demonstrated potential to enhance drug delivery in preclinical models. Here, we investigated the ability of one class of heat-generating nanomaterials called [...]

Menée à l'aide de xénogreffes de cancer du pancréas, cette étude met en évidence l'activité antitumorale d'un inhibiteur de la lactate déshydrogénase A (FX11) en l'absence d'expression du gène TP53

Therapeutic targeting of the Warburg effect in pancreatic cancer relies on an absence of p53 function

Rajeshkumar, N.V. ; Dutta, Prasanta ; Yabuuchi, Shinichi ; de Wilde, Roeland F ; Matrinez, Gary V ; Le, Anne ; Kamphorst, Jurre J ; Rabinowitz, Joshua D ; Jain, Sanjay K ; Hidalgo, Manuel ; Dang, Chi V ; Gillies, Robert J ; Maitra, Anirban

The "Warburg effect" describes a peculiar metabolic feature of many solid tumors, namely their high glycolytic activity for biosynthesis and an inefficient generation of ATP. During aerobic glycolysis, pyruvate is preferentially metabolized to lactate by the enzyme lactate dehydrogenase-A (LDH-A), suggesting a possible vulnerability at this target for small molecule inhibition in cancer cells. In this study, we used FX11, a small molecule inhibitor of LDH-A, to investigate this possible [...]

Menée in vitro et in vivo sur des modèles de cancer du poumon avec réarrangements ALK, cette étude met en évidence l'activité antitumorale d'un composé appelé PF-06463922, un inhibiteur d'ALK/ROS1, et suggère son intérêt pour surmonter une résistance aux premières générations d'inhibiteurs d'ALK

PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models

Zou, Helen Y ; Friboulet, Luc ; Kodack, David P ; Engstrom, Lars D ; Li, Qiuhua ; West, Melissa ; Tang, Ruth W ; Wang, Hui ; Tsaparikos, Konstantinos ; Wang, Jinwei ; Timofeevski, Sergei ; Katayama, Ryohei ; Dinh, Dac M ; Lam, Hieu ; Lam, Justine L ; Yamazaki, Shinji ; Hu, Wenyue ; Patel, Bhushankumar ; Bezwada, Divya ; Frias, Rosa L ; Lifshits, Eugene ; Mahmood, Sidra ; Gainor, Justin F ; Affolter, Timothy ; Lappin, Patrick B ; Gukasyan, Hovhannes ; Lee, Nathan ; Deng, Shibing ; Jain, Rakesh K ; Johnson, Ted W ; Shaw, Alice T ; Fantin, Valeria R ; Smeal, Tod

We report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF-06463922 displayed superior potency against all known clinically acquired ALK mutations, including the highly resistant G1202R mutant. Furthermore, PF-06463922 treatment led to regression of EML4-ALK-driven brain metastases, leading to prolonged mouse survival, in a superior manner. Finally, PF-06463922 demonstrated high selectivity [...]

Menée sur des lignées cellulaires de cancer du poumon non à petites cellules, cette étude met en évidence des mécanismes par lesquels, en induisant une transition épithélio-mésenchymateuse, l'amplification du gène SMO et la voie de signalisation Hedgehog favorisent une résistance aux thérapies ciblées anti EGFR

SMO gene amplification and activation of the hedgehog pathway as novel mechanisms of resistance to anti-epidermal growth factor receptor drugs in human lung cancer

Della Corte, Carminia Maria ; Bellevicine, Claudio ; Vicidomini, Giovanni ; Vitagliano, Donata ; Malapelle, Umberto ; Accardo, Marina ; Fabozzi, Alessio ; Fiorelli, Alfonso ; Fasano, Morena ; Papaccio, Federica ; Martinelli, Erika ; Troiani, Teresa ; Troncone, Giancarlo ; Santini, Mario ; Bianco, Roberto ; Ciardiello, Fortunato ; Morgillo, Floriana

Purpose: Resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) is often related to activation of other signaling pathways and evolution through a mesenchymal phenotype. Experimental Design: Since Hedgehog (Hh) pathway has emerged as an important mediator of epithelial-to-mesenchymal transition (EMT), we studied the activation of Hh signaling in models of EGFR TKIs intrinsic or acquired resistance from both EGFR mutated and wild-type (WT) non small cell lung [...]

Cet article passe en revue les travaux récents sur le rôle des mutations du gène ESR1, codant le récepteur alpha des estrogènes, dans la résistance aux hormonothérapies chez les patientes atteintes d'un cancer du sein

ESR1 mutations - a mechanism for acquired endocrine resistance in breast cancer

Jeselsohn, Rinath ; Buchwalter, Gilles ; Angelis, Carmine De ; Brown, Myles ; Schiff, Rachel

Approximately 70% of breast cancers are oestrogen receptor [alpha] (ER) positive, and are, therefore, treated with endocrine therapies. However, about 25% of patients with primary disease and almost all patients with metastases will present with or eventually develop endocrine resistance. Despite the magnitude of this clinical challenge, the mechanisms underlying the development of resistance remain largely unknown. In the past 2 years, several studies unveiled gain-of-function mutations in [...]

Menée à l'aide d'un modèle murin de cancer du col de l'utérus, cette étude met en évidence des mécanismes par lesquels la rapamycine amoindrit la réponse antitumorale des lymphocytes T associée à un vaccin peptidique (CyaA-E7)

Rapamycin impairs antitumor CD8+ T cell responses and vaccine-induced tumor eradication

Chaoul, Nada ; Fayolle, Catherine ; Desrues, Belinda ; Oberkampf, Marine ; Tang, Alexandre ; Ladant, Daniel ; Leclerc, Claude

The metabolic sensor mTOR broadly regulates cell growth and division in cancer cells, leading to a significant focus on studies of rapamycin and its analogs as candidate anti-cancer drugs. However, mTOR inhibitors have failed to produce useful clinical efficacy, potentially because mTOR is also critical in T cells implicated in immune surveillance. Indeed, recent studies using rapamycin have demonstrated the important role of mTOR in differentiation and induction of the CD8+ memory in T cell [...]

Menée sur des lignées cellulaires de carcinome épidermoïde de la tête et du cou, cette étude met en évidence une importante variabilité de la réponse cellulaire lorsqu'une thérapie ciblée anti EGFR est ajoutée à du cisplatine

STAT1 Activation is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells

Schmitt, Nicole C. ; Trivedi, Sumita ; Ferris, Robert L.

Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGFR inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefit from the use of these two drugs in combination. Possible explanations for this include overlapping downstream signaling cascades. Using in vitro studies, we tested the hypothesis that cisplatin [...]

Mené sur 71 patients atteints d'une leucémie lymphocytaire chronique, cet essai évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout d'ofatumumab à l'ibrutinib selon trois protocoles d'administration

Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study

Jaglowski, Samantha M. ; Jones, Jeffrey A. ; Nagar, Veena ; Flynn, Joseph M. ; Andritsos, Leslie A. ; Maddocks, Kami J. ; Woyach, Jennifer A. ; Blum, Kristie A. ; Grever, Michael R. ; Smucker, Kelly ; Ruppert, Amy S. ; Heerema, Nyla A. ; Lozanski, Gerard ; Stefanos, Mona ; Munneke, Brian ; West, Jamie-Sue ; Neuenburg, Jutta K. ; James, Danelle F. ; Hall, Nathan ; Johnson, Amy J. ; Byrd, John C.

Ibrutinib combined with ofatumumab in relapsed CLL had had an ORR of 83% with median time to response of less than 3 months in all groups.All 3 sequences of administration were acceptably tolerated and active; responses were durable and median PFS was not yet reached. Ibrutinib represents a therapeutic advance in CLL but as monotherapy produces few complete remissions in previously treated patients. Anti-CD20 antibodies have improved response and progression-free survival when combined with [...]

A partir de données du système de notification d'événements indésirables à la Food and Drug Administration, cette étude analyse la toxicité rénale de deux inhibiteurs de BRAF, le vémurafénib et le dabrafénib, chez les patients atteints d'un mélanome métastatique présentant la mutation V600E du gène BRAF

Nephrotoxicity of the BRAF inhibitors vemurafenib and dabrafenib

Jhaveri, K. D. ; Sakhiya, V. ; Fishbane, S.

Importance : The selective BRAF inhibitors vemurafenib and dabrafenib have shown significant improvement in patient survival compared with standard therapy in BRAF V600–mutant metastatic melanoma. Observations : We reviewed Food and Drug Administration Adverse Event Reporting System (FAERS) data for both agents for renal toxic effects. From July 2011 through June 2014, 132 cases of acute kidney injury in patients receiving vemurafenib therapy were reported. Renal injury was more common in men [...]

Mené sur 265 patients atteints d'un cancer du poumon EGFR+ de stade avancé, cet essai international de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de géfinitib à une chimiothérapie après un traitement de première ligne à base de géfitinib

Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial

Soria, Jean-Charles ; Wu, Yi-Long ; Nakagawa, Kazuhiko ; Kim, Sang-We ; Yang, Jin-ji ; Ahn, Myung-Ju ; Wang, Jie ; Yang, James Chih-Hsin ; Lu, You ; Atagi, Shinji ; Ponce, Santiago ; Lee, Dae Ho ; Liu, Yunpeng ; Yoh, Kiyotaka ; Zhou, Jian-Ying ; Shi, Xiaojin ; Webster, Alan ; Jiang, Haiyi ; Mok, Tony S. K.

Background : Optimum management strategies for patients with advanced non-small-cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine-kinase inhibitors are undefined. We aimed to assess the efficacy and safety of continuing gefitinib combined with chemotherapy versus chemotherapy alone in patients with EGFR-mutation-positive advanced NSCLC with acquired resistance to first-line gefitinib. Methods : The randomised, phase 3, multicentre IMPRESS study was done in 71 centres in 11 [...]

Mené sur 24 patients atteints d'un carcinome métastatique à cellules rénales, cet essai de phase I/II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement combinant S-1 et sorafénib

Phase 1/2 study of S-1 in combination with sorafenib for metastatic renal cell carcinoma

Naito, S. ; Sakai, H. ; Hashine, K. ; Tomita, T. ; Shinohara, N. ; Fujisawa, M. ; Eto, M. ; Ozono, S. ; Akaza, H.

Background : The potential of S-1 for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase 2 studies. We aimed to assess the safety, tolerance, pharmacokinetics and clinical activity of S-1 combined with sorafenib in patients with mRCC. Patients and methods : In this multicenter, single-arm, open-label, phase 1/2 study of S-1 plus sorafenib, we recruited patients with clear-cell or papillary renal cell carcinoma who had received a maximum of one prior [...]

Menée in vitro et à l'aide de xénogreffes de cancer du poumon ou de cancer de la tête et du cou, cette étude évalue les effets d'un anticorps spécifique ciblant les récepteurs EGFR et HER3 sur la réponse des cellules tumorales aux rayonnements ionisants

Antitumor effects of MEHD7945A, a dual specific antibody against EGFR and HER3, in combination with radiation in lung and head and neck cancers

Li, Chunrong ; Huang, Shyhmin ; Armstrong, Eric A. ; Francis, David M. ; Werner, Lauryn R ; Sliwkowski, Mark X. ; Kogel, Albert van der ; Harari, Paul M.

HER receptor family members (EGFR, HER2, HER3 and HER4) play important roles in tumorigenesis and response to cancer therapeutics. In the current study, we evaluated the capacity of the dual-target antibody MEHD7945A that simultaneously targets EGFR and HER3 to modulate radiation response in lung and head and neck cancer models. Antitumor effects of MEHD7945A in combination with radiation were evaluated in cell culture and tumor xenograft models. Mechanisms that may contribute to increased [...]

Mené sur 437 patients atteints d'un cancer du poumon non à petites cellules inopérable de stade III et traités entre 2005 et 2011, cet essai multicentrique de phase III évalue, du point de vue de la survie sans progression et de la survie globale, l'intérêt d'une chimiothérapie de consolidation par docétaxel-cisplatine après un traitement combinant une chimiothérapie, utilisant les mêmes agents anticancéreux, et une radiothérapie concomitante

Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non–Small-Cell Lung Cancer: KCSG-LU05-04

Ahn, Jin Seok ; Ahn, Yong Chan ; Kim, Joo-Hang ; Lee, Chang Geol ; Cho, Eun Kyung ; Lee, Kyu Chan ; Chen, Ming ; Kim, Dong-Wan ; Kim, Hoon-Kyo ; Min, Young Joo ; Kang, Jin-Hyoung ; Choi, Jin-Hyuck ; Kim, Sang-We ; Zhu, Guangying ; Wu, Yi-Long ; Kim, Sung Rok ; Lee, Kyung Hee ; Song, Hong Suk ; Choi, Yoon-La ; Sun, Jong-Mu ; Jung, Sin-Ho ; Ahn, Myung-Ju ; Park, Keunchil

Purpose : To determine the efficacy of consolidation chemotherapy (CC) with docetaxel and cisplatin (DP) after concurrent chemoradiotherapy (CCRT) with the same agents in locally advanced non–small-cell lung cancer (LA-NSCLC). Patient and Methods : Patients were randomly assigned to either CCRT alone (observation arm) or CCRT followed by CC (consolidation arm). CCRT with docetaxel (20 mg/m2) and cisplatin (20 mg/m2) was administered every week for 6 weeks with a total dose of 66 Gy of thoracic [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude évalue l'intérêt de combiner rayons X et nanotubes de carbone chargés en catéchines pour détruire les cellules souches de cancer de la prostate

Development of novel radiochemotherapy approaches targeting prostate tumor progenitor cells using nanohybrids

Castro Nava, Arturo ; Cojoc, Monica ; Peitzsch, Claudia ; Cirillo, Giuseppe ; Kurth, Ina ; Fuessel, Susanne ; Erdmann, Kati ; Kunhardt, David ; Vittorio, Orazio ; Hampel, Silke ; Dubrovska, Anna

Many tumors including prostate cancer are maintained by cancer stem cells (CSCs), which might cause tumor relapse if not eradicated during the course of treatment. Specific targeting or radiosensitization of CSCs bear promise to improve tumor curability by synergistic effects in combination with radiotherapy. Carbon nanotubes (CNTs) can be used as promising drug delivery systems for anticancer drugs such as the flavonoid catechin. Catechin is an extensively studied active ingredient of the [...]

Menée sur un modèle murin de carcinome du côlon, cette étude évalue l'intérêt de bactériochlorines, des photosensibilisants, pour améliorer l'efficacité d'une photothérapie dynamique contre la croissance tumorale et la survenue de métastases pulmonaires

Elimination of primary tumours and control of metastasis with rationally designed bacteriochlorin photodynamic therapy regimens

Rocha, Luis B. ; Gomes-da-Silva, Lígia C. ; Dąbrowski, Janusz M. ; Arnaut, Luis G.

Photodynamic therapy (PDT) with current photosensitisers focuses on local effects and these are limited by light penetration in tissues. We employ a stable near-infrared (NIR) absorbing bacteriochlorin with ca. 8 h plasma half-life to increase the depth of the treatment and elicit strong systemic (immune) responses. Primary tumour growth delays and cures of BALB/c and nude mice bearing CT26 mouse colon carcinoma are related to the parameters that control PDT efficacy. The systemic anti-tumour [...]

Menée à partir des données d'un essai de phase III portant sur 349 patients atteints d'un glioblastome récemment diagnostiqué, cette étude montre que l'ajout du bévacizumab à un traitement combinant radiothérapie de première ligne et témozolomide améliore la survie globale des patients présentant un glioblastome proneural

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial

Sandmann, Thomas ; Bourgon, Richard ; Garcia, Josep ; Li, Congfen ; Cloughesy, Timothy ; Chinot, Olivier L. ; Wick, Wolfgang ; Nishikawa, Ryo ; Mason, Warren ; Henriksson, Roger ; Saran, Frank ; Lai, Albert ; Moore, Nicola ; Kharbanda, Samir ; Peale, Franklin ; Hegde, Priti ; Abrey, Lauren E. ; Phillips, Heidi S. ; Bais, Carlos

Purpose : The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular [...]

Cet article analyse les perspectives offertes par un nouveau critère de jugement intermédiaire pour prendre en compte la dynamique spécifique de l'activité antitumorale des inhibiteurs de points de contrôle immunitaire et évaluer leur efficacité dans les essais cliniques

Milestone Survival: A Potential Intermediate Endpoint for Immune Checkpoint Inhibitors

Chen, Tai-Tsang

Recent advancements in cancer immunotherapies offer diverse strategies for cancer treatment. Among the most promising approaches is the blockade of immune checkpoint molecules to activate antitumor immunity. With targeted immunotherapies of new mechanisms of action come greater challenges in study design and statistical analysis, as well as the need for refining clinical trial endpoints. The long-term survival and delayed clinical effects demonstrated by these therapies could result in [...]