A partir d'une revue de la littérature (49 publications), cet article compare l'efficacité et la sécurité de différentes techniques conservatrices pour traiter un cancer du pénis

Penile cancer: organ-sparing techniques

Hegarty, Paul K. ; Eardley, Ian ; Heidenreich, Axel ; McDougal, W. Scott ; Minhas, Suks ; Spiess, Philippe E. ; Watkin, Nick ; Horenblas, Simon

To compare the oncological safety of treating patients with penile cancer with conservative techniques developed to preserve function, cosmesis and psychological well-being with more radical ablative strategies. We conducted an extensive review of the literature of penile-preserving and ablative techniques and report on the oncological as well as functional outcomes. There were no randomised studies comparing penile-preserving and ablative techniques. Most studies consisted of retrospective [...]

Menée à partir de données portant sur 77 patients présentant des métastases uvéales traitées entre 2002 et 2012 (durée médiane de suivi : 7,7 mois), cette étude évalue l'efficacité, du point de vue du contrôle local de la maladie, et les effets secondaires d'une protonthérapie ciblant l'uvée

Outcomes of Proton Therapy for the Treatment of Uveal Metastases

Kamran, Sophia C. ; Collier, John M. ; Lane, Anne Marie ; Kim, Ivana ; Niemierko, Andrzej ; Chen, Yen-Lin E. ; MacDonald, Shannon M. ; Munzenrider, John E. ; Gragoudas, Evangelos ; Shih, Helen A.

Purpose/Objective(s) : Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials : A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy [...]

Menée à partir de données portant sur 193 patients atteints d'un cancer du poumon à petites cellules traité par résection complète entre 2003 et 2009, cette étude chinoise évalue, du point de vue des taux de survie globale à 2 et 5 ans, l'intérêt d'une radiothérapie crânienne prophylactique

Prophylactic cranial irradiation improved the overall survival of patients with surgically resected small cell lung cancer, but not for stage I disease

Zhu, Hui ; Guo, Hongbo ; Shi, Fang ; Zhu, Kunli ; Luo, Jingyu ; Liu, Xibin ; Kong, Li ; Yu, Jingming

Objectives : We conducted a retrospective study to evaluate the role of prophylactic cranial irradiation (PCI) on patients with surgically resected small cell lung cancer (SCLC). Patients and Methods : Between January 2003 and December 2009, the records of completely resected patients who were diagnosed with SCLC and definitive pTNM stage on the basis of histological proof were reviewed. According to the therapy modality, patients were allocated to PCI group and non-PCI group. Results : A total [...]

Menée à partir des données de l'association britannique des chirurgiens urologues sur l'année 2011 (2 163 prostatectomies radicales réalisées), cette étude analyse les pratiques actuelles en matière de prostatectomie radicale et compare la performance des différentes techniques

Contemporary practice and technique-related outcomes for radical prostatectomy in the UK: a report of national outcomes

Laird, Alexander ; Fowler, Sarah ; Good, Daniel W. ; Stewart, Grant D. ; Srinivasan, Vaikuntam ; Cahill, Declan ; Brewster, Simon F. ; McNeill, S. Alan ; British Association of Urological, Surgeons

Objective : To determine current radical prostatectomy (RP) practice in the UK and compare surgical outcomes between techniques. Patients and Methods : All RPs performed between 1 January 2011 and 31 December 2011 in the UK with data entered into the British Association of Urological Surgeons (BAUS) database, were identified for analysis. Overall surgical outcomes were assessed and subgroup analyses of these outcomes, based on operative technique [open RP (ORP), laparoscopic RP (LRP) and [...]

Menée sur 20 patientes atteintes d'un cancer du sein, cette étude évalue, par rapport à une radiothérapie tangentielle avec modulation d'intensité, l'intérêt d'une irradiation du sein entier par protonthérapie avec modulation d'intensité pour réduire au maximum la dose de rayonnements atteignant le coeur et la branche descendante de l'artère coronaire gauche

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

Mast, MirjamE ; Vredeveld, ElineJ ; Credoe, HermanM ; van Egmond, Jaap ; Heijenbrok, MarkW ; Hug, EugenB ; Kalk, Patrick ; van Kempen-Harteveld, LoesM L. ; Korevaar, ErikW ; van der Laan, HansPaul ; Langendijk, JohannesA ; Rozema, HansJ E. ; Petoukhova, AnnaL ; Schippers, JacobusM ; Struikmans, Henk ; Maduro, JohnH

Purpose : In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. Methods : In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a [...]

Cet article passe en revue les travaux récents ouvrant la voie au développement de thérapies ciblées sur les oncoprotéines RAS

Drugging the undruggable RAS: Mission Possible?

Cox, Adrienne D. ; Fesik, Stephen W. ; Kimmelman, Alec C. ; Luo, Ji ; Der, Channing J.

Despite more than three decades of intensive effort, no effective pharmacological inhibitors of the RAS oncoproteins have reached the clinic, prompting the widely held perception that RAS proteins are 'undruggable'. However, recent data from the laboratory and the clinic have renewed our hope for the development of RAS-inhibitory molecules. In this Review, we summarize the progress and the promise of five key approaches. Firstly, we focus on the prospects of using direct inhibitors of RAS. [...]

Cet article passe en revue les nouvelles approches pour le traitement d'une leucémie myéloïde aiguë

New Strategies in Acute Myelogenous Leukemia: Leukemogenesis and Personalized Medicine

Gojo, Ivana ; Karp, Judith E

Recent advances in molecular technology have unraveled the complexity of leukemogenesis and provided the opportunity to design more personalized and pathophysiology-targeted therapeutic strategies. Despite the use of intensive chemotherapy, relapse remains the most common cause for therapeutic failure in acute myelogenous leukemia (AML). The interactions between leukemia stem cells (LSC) and marrow microenvironment appear to be critical in promoting therapeutic resistance through progressive [...]

Menée sur des lignées cellulaires de lymphome anaplasique à grandes cellules, cette étude met en évidence des mécanismes par lesquels le vorinostat, un inhibiteur d'histone désacétylase, réduit l'efficacité du brentuximab vedotin

Vorinostat Downregulates CD30 and Decreases Brentuximab Vedotin Efficacy in Human Lymphocytes

Hasanali, Zainul S. ; Epner, Elliot M. ; Feith, David J ; Loughran, Thomas P ; Sample, Clare E

With an increasing number of clinical trials looking at combination therapies in cancer, potential drug-drug interactions require particular attention. One such instance is the treatment of CD30+ tumors after previous vorinostat (SAHA) failure with the anti-CD30 antibody-drug conjugate brentuximab vedotin. Using B-, T- and NK-cell lines in vitro, we demonstrate that SAHA downregulates the expression of CD30 and lowers the efficacy of subsequent brentuximab vedotin treatment if baseline CD30 [...]

Menée sur des lignées cellulaires, cette étude identifie des mutations ponctuelles dans les gènes ERK1 et ERK2 en association avec la résistance à des inhibiteurs de la voie de signalisation MAPK

ERK mutations confer resistance to mitogen-activated protein kinase pathway inhibitors

Goetz, Eva M ; Ghandi, Mahmoud ; Treacy, Daniel J ; Wagle, Nikhil ; Garraway, Levi A

The use of targeted therapeutics directed against BRAFV600-mutant metastatic melanoma improves progression free survival in many patients; however, acquired drug resistance remains a major medical challenge. By far the most common clinical resistance mechanism involves reactivation of the MAPK (RAF/MEK/ERK) pathway by a variety of mechanisms. Thus, targeting ERK itself has emerged as an attractive therapeutic concept, and several ERK inhibitors have entered clinical trials. We sought to [...]

Menée sur des lignées cellulaires et à l'aide de xénogreffes de cancer du poumon, cette étude analyse l'activité antitumorale d'un composé appelé OTS964, un inhibiteur de l'activité kinase de TOPK

TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis

Matsuo, Yo ; Park, Jae-Hyun ; Miyamoto, Takashi ; Yamamoto, Shinji ; Hisada, Shoji ; Alachkar, Houda ; Nakamura, Yusuke

TOPK (T–lymphokine-activated killer cell–originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. We report the development of a potent TOPK inhibitor, OTS964 {(R)-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one}, which inhibits TOPK kinase activity with high affinity and selectivity. Similar to the [...]

Mené sur 55 patients atteints d'une tumeur solide de stade avancé, cet essai de phase I avec escalade de dose évalue la doxe maximale tolérée et l'activité antitumorale du demcizumab, un anticorps monoclonal anti DLL4

A Phase 1 Dose Escalation and Expansion Study of the Anti-Cancer Stem Cell Agent Demcizumab (Anti-DLL4) in Patients with Previously Treated Solid Tumors

Smith, David C ; Eisenberg, Peter D. ; Manikhas, George M ; Chugh, Rashmi ; Gubens, Matthew A ; Stagg, Robert J ; Kapoun, Ann M. ; Xu, Lu ; Dupont, Jakob ; Sikic, Branimir I.

Purpose: This Phase I trial evaluated the safety, pharmacokinetics, pharmacodynamics and of demcizumab (OMP-21M18), a humanized IgG2 monoclonal antibody targeting the Notch ligand DLL4 in adult patients with advanced malignancies. Methods: Standard 3+3 design, with demcizumab 0.5, 1, 2.5, or 5 mg/kg weekly or 2.5, 5 or 10 mg/kg every other week, with an expansion cohort at 10 mg/kg every other week. Dose-limiting toxicities (DLT) were assessed during the first 28 days. Results: Fifty-five [...]

A partir d'échantillons prélevés sur 1 115 patients atteints d'une tumeur de stade avancé et inclus dans un essai de phase I au Centre MD Anderson, cette étude évalue la prévalence des tumeurs présentant une amplification du gène MET, puis analyse, pour les patients concernés, la réponse à un inhibiteur de c-MET

Analysis of 1,115 patients tested for MET amplification and therapy response in the MD Anderson Phase I clinic

Fontes Jardim, Denis L ; Tang, Chad ; De Melo-Gagliato, Debora ; Falchook, Gerald S. ; Hess, Kenneth R. ; Janku, Filip ; Fu, Siqing ; Wheler, Jennifer J. ; Zinner, Ralph G. ; Naing, Aung ; Tsimberidou, Apostolia M. ; Holla, Vijaykumar R ; Li, Marilyn M ; Roy Chowdhuri, Sinchita ; Luthra, Rajyalakshmi ; Salgia, Ravi ; Kurzrock, Razelle ; Meric-Bernstein, Funda ; Hong, David

Purpose: Assess MET amplification among different cancers, association with clinical factors and genetic aberrations and targeted therapy response modifications. Experimental Design: From 05/2010 to 11/2012 samples from patients with advanced tumors referred to the Phase I Clinic were analyzed for MET gene amplification by fluorescence in situ hybridization. Patient demographic, histologic, molecular characteristics and outcomes in phase I protocols were compared per MET amplification status. [...]

Menée sur un patient atteint d'un mélanome de stade IV présentant la mutation V600E du gène BRAF, puis sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes permettant de rendre compte du développement d'une leucémie lymphocytaire chronique pendant un traitement à l'aide de vemurafenib

BRAF inhibitor–associated ERK activation drives development of chronic lymphocytic leukemia

Yaktapour, Niuscha ; Meiss, Frank ; Mastroianni, Justin ; Zenz, Thorsten ; Andrlová, Hana ; Mathew, Nimitha R. ; Claus, Rainer ; Hutter, Barbara ; Frohling, Stefan ; Brors, Benedikt ; Pfeifer, Dietmar ; Pantic, Milena ; Bartsch, Ingrid ; Spehl, Timo S. ; Meyer, Philipp T. ; Duyster, Justus ; Zirlik, Katja ; Brummer, Tilman ; Zeiser, Robert

Patients with BRAFV600E/K-driven melanoma respond to the BRAF inhibitor vemurafenib due to subsequent deactivation of the proliferative RAS/RAF/MEK/ERK pathway. In BRAF WT cells and those with mutations that activate or result in high levels of the BRAF activator RAS, BRAF inhibition can lead to ERK activation, resulting in tumorigenic transformation. We describe a patient with malignant melanoma who developed chronic lymphocytic leukemia (CLL) in the absence of RAS mutations during vemurafenib [...]

Mené sur 64 patients atteints d'un lymphome diffus à grandes cellules B récemment diagnostiqué, cet essai de phase II évalue l'efficacité de l'ajout de lénalidomide à un protocole R-CHOP (rituximab plus cyclophosphamide, doxorubicine, vincristine et prednisone)

Lenalidomide Combined With R-CHOP Overcomes Negative Prognostic Impact of Non–Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study

Nowakowski, Grzegorz S. ; LaPlant, Betsy ; Macon, William R. ; Reeder, Craig B. ; Foran, James M. ; Nelson, Garth D. ; Thompson, Carrie A. ; Rivera, Candido E. ; Inwards, David J. ; Micallef, Ivana N. ; Johnston, Patrick B. ; Porrata, Luis F. ; Ansell, Stephen M. ; Gascoyne, Randy D. ; Habermann, Thomas M. ; Witzig, Thomas E.

Purpose : Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods : Eligible patients were adults with newly diagnosed untreated stages II [...]

Mené sur 432 patients atteints d'un mélanome à haut risque, cet essai de phase III compare l'efficacité, du point de vue de la survie sans récidive et de la survie globale, et la toxicité d'un traitement adjuvant de référence (interféron alpha à haute dose pendant un an) et d'une biochimiothérapie de plus courte durée combinant 3 cycles, à 21 jours d'intervalle, de dacarbazine, cisplatine, vinblastine, interleukine-2, interféron alpha-2b et facteur stimulant la croissance des colonies de granulocytes

Southwest Oncology Group S0008: A Phase III Trial of High-Dose Interferon Alfa-2b Versus Cisplatin, Vinblastine, and Dacarbazine DTIC, Plus Interleukin-2 and Interferon in Patients With High-Risk Melanoma—An Intergroup Study of Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group

Flaherty, Lawrence E. ; Othus, Megan ; Atkins, Michael B. ; Tuthill, Ralph J. ; Thompson, John A. ; Vetto, John T. ; Haluska, Frank G. ; Pappo, Alberto S. ; Sosman, Jeffrey A. ; Redman, Bruce G. ; Moon, James ; Ribas, Antoni ; Kirkwood, John M. ; Sondak, Vernon K.

Purpose : High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration–approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective. Patients and Methods : S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients [...]

Mené sur 508 patients atteints d'un cancer colorectal métastatique, cet essai de phase III évalue compare l'efficacité, du point de vue de la survie sans progression, et la toxicité d'une combinaison FOLFOXIRI-bevacizumab et d'une combinaison FOLFIRI-bevacizumab

Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer

Loupakis, Fotios ; Cremolini, Chiara ; Masi, Gianluca ; Lonardi, Sara ; Zagonel, Vittorina ; Salvatore, Lisa ; Cortesi, Enrico ; Tomasello, Gianluca ; Ronzoni, Monica ; Spadi, Rosella ; Zaniboni, Alberto ; Tonini, Giuseppe ; Buonadonna, Angela ; Amoroso, Domenico ; Chiara, Silvana ; Carlomagno, Chiara ; Boni, Corrado ; Allegrini, Giacomo ; Boni, Luca ; Falcone, Alfredo

BACKGROUND : A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed [...]

A partir d'une revue systématique de la littérature (40 publications identifiées), cet article analyse les résultats des essais de thérapies ciblées pour le traitement des patients atteints d'un cancer colorectal métastatique

Targeted Therapies in Metastatic Colorectal Cancer: A Systematic Review and Assessment of Currently Available Data

Kirstein, Martha M. ; Lange, Ansgar ; Prenzler, Anne ; Manns, Michael P. ; Kubicka, Stefan ; Vogel, Arndt

Background. Survival of patients with metastatic colorectal cancer (mCRC) has been significantly improved with the introduction of the monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel molecular-targeted agents such as aflibercept and regorafenib have recently been approved. The aim of this review is to summarize and assess the effects of molecular agents in mCRC based on the available phase II and III trials, [...]

Menée sur un total de 4 046 patientes atteintes d'un cancer du sein HER2+ de stade précoce, cette étude analyse les résultats à long terme de deux essais ayant évalué l'ajout de trastuzumab au paclitaxel après un traitement combinant doxorubicine et cyclophosphamide (durée médiane de suivi : 8,4 ans)

Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831

Perez, Edith A. ; Romond, Edward H. ; Suman, Vera J. ; Jeong, Jong-Hyeon ; Sledge, George ; Geyer, Charles E. ; Martino, Silvana ; Rastogi, Priya ; Gralow, Julie ; Swain, Sandra M. ; Winer, Eric P. ; Colon-Otero, Gerardo ; Davidson, Nancy E. ; Mamounas, Eleftherios ; Zujewski, Jo Anne ; Wolmark, Norman

Purpose : Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2) –positive breast cancer were first reported in 2005. One of these reports, the joint analysis of North Central Cancer Treatment Group NCCTG N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast and Bowel Project [...]

Cet article fait le point sur les agents thérapeutiques pouvant, dans le cadre d'une thérapie ciblée, être combinés avec une radiothérapie pour traiter différents types de sarcome des tissus mous

Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

Wong, Philip ; Houghton, Peter ; Kirsch, David G. ; Finkelstein, Steven E. ; Monjazeb, Arta M. ; Xu-Welliver, Meng ; Dicker, Adam P. ; Ahmed, Mansoor ; Vikram, Bhadrasain ; Teicher, Beverly A. ; Coleman, C. Norman ; Machtay, Mitchell ; Curran, Walter J. ; Wang, Dian

Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity [...]

Mené sur deux cohortes incluant respectivement 23 et 9 patients atteints d'un sarcome localisé des tissus mous, cet essai de phase Ib/II analyse l'effet de l'hypoxie tumorale sur la réponse thérapeutique, puis évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale à 2 ans, et la toxicité d'un traitement combinant sunitinib et radiothérapie pré-opératoire

A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma

Lewin, J. ; Khamly, K. K. ; Young, R. J. ; Mitchell, C. ; Hicks, R. J. ; Toner, G. C. ; Ngan, S. Y. K. ; Chander, S. ; Powell, G. J. ; Herschtal, A. ; Te Marvelde, L. ; Desai, J. ; Choong, P. F. M. ; Stacker, S. A. ; Achen, M. G. ; Ferris, N. ; Fox, S. ; Slavin, J. ; Thomas, D. M.

Background : Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can ‘normalise’ tumour vasculature, thereby improving oxygenation, remains unknown. Methods : Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer 18F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT [...]

Mené sur 57 patients atteints d'un rhabdomyosarcome (âge : 21 ans au plus ; durée médiane de suivi : 47 mois), cet essai de phase II évalue l'efficacité, du point de vue du contrôle local de la maladie, de la survie sans événement et de la survie globale à 5 ans, et la toxicité d'un traitement combinant une chimiothérapie et une protonthérapie

Preliminary Results of a Phase II Trial of Proton Radiotherapy for Pediatric Rhabdomyosarcoma

Ladra, Matthew M. ; Szymonifka, Jackie D. ; Mahajan, Anita ; Friedmann, Alison M. ; Yong Yeap, Beow ; Goebel, Claire P. ; MacDonald, Shannon M. ; Grosshans, David R. ; Rodriguez-Galindo, Carlos ; Marcus, Karen J. ; Tarbell, Nancy J. ; Yock, Torunn I.

Purpose : This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS). Patients and Methods : Fifty-seven patients with localized RMS (age 21 years or younger) or metastatic embryonal RMS (age 2 to 10 years) were enrolled between February 2005 and August 2012. All patients were treated with chemotherapy based on either vincristine, actinomycin, and [...]

Menée à partir d'échantillons sériques prélevés sur 18 patients atteints d'un cancer oropharyngé de stade III-IV associé au papillomavirus humain, cette étude met en évidence une augmentation de l'expression de PD1 sur les lymphocytes T CD4+ et une diminution de la réponse immunitaire spécifique après chimioradiothérapie

Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer

Parikh, Falguni ; Duluc, Dorothee ; Imai, Naoko ; Clark, Amelia ; Misiukiewicz, Krzys ; Bonomi, Marcello ; Gupta, Vishal ; Patsias, Alexis ; Parides, Michael ; Demicco, Elizabeth G. ; Zhang, David Y ; Kim-Schulze, Seunghee ; Kao, Johnny ; Gnjatic, Sacha ; Oh, Sangkon ; Posner, Marshall ; Sikora, Andrew G.

While viral antigens in HPV-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from stage III-IV OPC patients undergoing concomitant chemoradiotherapy (CRT) with or without induction chemotherapy. Circulating immunocytes including CD4+ and CD8+ T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by [...]

Cet article plaide pour une nouvelle approche des essais cliniques qui, prenant en compte l'hétérogénéité des tumeurs, évaluent des combinaisons individualisées de traitements pour chaque patient

Unique Molecular Landscapes in Cancer: Implications for Individualized, Curated Drug Combinations

Wheler, Jennifer J. ; Lee, J. Jack ; Kurzrock, Razelle

With increasingly sophisticated technologies in molecular biology and 'omic' platforms to analyze patients' tumors, more molecular diversity and complexity in cancer are being observed. Recently, we noted unique genomic profiles in a group of patients with metastatic breast cancer based on an analysis with next generation sequencing (NGS); amongst 57 consecutive patients, no two had the same molecular portfolio (1). Applied genomics therefore appears to represent a disruptive innovation in that [...]