Menée auprès d'enfants atteints d'une leucémie lymphoblastique à cellules B avec risque de récidive élevé, cette étude évalue l'intérêt d'ajouter à des injections intratéchales de méthotrexate des injections intratéchales d'hydrocortisone et de cytarabine pour améliorer la survie sans maladie à 5 ans

Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children’s Oncology Group Study AALL1131

Salzer, Wanda L. ; Burke, Michael J. ; Devidas, Meenakshi ; Dai, Yunfeng ; Hardy, Kristina K. ; Kairalla, John A. ; Gore, Lia ; Hilden, Joanne M. ; Larsen, Eric ; Rabin, Karen R. ; Zweidler-McKay, Patrick A. ; Borowitz, Michael J. ; Wood, Brent ; Heerema, Nyla A. ; Carroll, Andrew J. ; Winick, Naomi ; Carroll, William L. ; Raetz, Elizabeth A. ; Loh, Mignon L. ; Hunger, Stephen P.

PURPOSE : The high-risk stratum of Children’s Oncology Group Study AALL1131 was designed to test the hypothesis that postinduction CNS prophylaxis with intrathecal triple therapy (ITT) including methotrexate, hydrocortisone, and cytarabine would improve the postinduction 5-year disease-free survival (DFS) compared with intrathecal methotrexate (IT MTX), when given on a modified augmented Berlin-Frankfurt-Münster backbone. PATIENTS AND METHODS : Children with newly diagnosed National Cancer [...]

Menée à partir d'une revue de la littérature publiée entre 2007 et 2017 (43 articles, 154 981 patients), cette méta-analyse évalue l'effet de complications infectieuses post-opératoires sur la survie des patients atteints d'un cancer colorectal traité par chirurgie

Meta-analysis of the impact of postoperative infective complications on oncological outcomes in colorectal cancer surgery

Lawler, J. ; Choynowski, M. ; Bailey, K. ; Bucholc, M. ; Johnston, A. ; Sugrue, M.

Background : Cancer outcomes are complex, involving prevention, early detection and optimal multidisciplinary care. Postoperative infection and surgical site‐infection (SSI) are not only uncomfortable for patients and costly, but may also be associated with poor oncological outcomes. A meta‐analysis was undertaken to assess the oncological effects of SSI in patients with colorectal cancer. Methods : An ethically approved PROSPERO‐registered meta‐analysis was conducted following PRISMA [...]

Menée à partir de données portant sur 134 patients atteints d'un carcinome à cellules rénales de stade I, cette étude évalue l'efficacité, du point de vue de la survie spécifique, de la survie sans récidive et de la survie globale à 10 ans, d'une cryoablation percutanée par rapport à une néphrectomie partielle et une néphrectomie radicale

Percutaneous Cryoablation for Stage 1 Renal Cell Carcinoma: Outcomes from a 10-year Prospective Study and Comparison with Matched Cohorts from the National Cancer Database

Morkos, John ; Porosnicu Rodriguez, Kori A. ; Zhou, Alice ; Kolarich, Andrew R. ; Frangakis, Constantine ; Rodriguez, Ronald ; Georgiades, Christos S.

Background : Percutaneous cryoablation (PCA) is an increasingly utilized treatment for stage I renal cell carcinoma (RCC), albeit without supportive level I evidence. Purpose : Primary objective was to determine the 10-year oncologic outcomes of PCA for stage I RCC in a prospective manner. Secondary objectives were to compare outcomes after partial nephrectomy (PN) and radical nephrectomy (RN) from the National Cancer Database (NCDB), to determine long-term renal function, and to determine the [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt de nanoparticules délivrant des oligonucléotides CpG capables, en se liant au récepteur TLR9, de supprimer la croissance tumorale et d'améliorer l'efficacité d'inhibiteurs de point de contrôle immunitaire

Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics

Buss, Colin G. ; Bhatia, Sangeeta N.

Checkpoint inhibitor (CPI) immunotherapies have revolutionized the treatment of a wide array of cancers, but their utility remains limited to a subset of patients with favorable disease phenotypes. We show that the generation of peptide-based nanocomplexes carrying immunostimulatory oligonucleotides dramatically increases the potency of certain of these compounds to stimulate toll-like receptor signaling. The administration of immunostimulatory nanocomplexes carrying CpG oligonucleotides [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'une stratégie thérapeutique consistant à cibler non pas des néo-antigènes issus de mutations génétiques mais des antigènes tumoraux induits par l'inhibition de l'expression du transporteur de peptides TAP

Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors

Garrido, Greta ; Schrand, Brett ; Levay, Agata ; Rabasa, Ailem ; Ferrantella, Anthony ; Da Silva, Diane M. ; Eramo, Francesca ; Marijt, Koen A. ; Zhang, Zhuoran ; Kwon, Deukwoo ; Kortylewski, Marcin ; Kast, W. Martin ; Dudeja, Vikas ; van Hall, Thorbald ; Gilboa, Eli

Vaccination of patients against neoantigens expressed in concurrent tumors, recurrent tumors, or tumors developing in individuals at risk of cancer is posing major challenges in terms of which antigens to target and is limited to patients expressing neoantigens in their tumors. Here, we describe a vaccination strategy against antigens that were induced in tumor cells by downregulation of the peptide transporter associated with antigen processing (TAP). Vaccination against TAP [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence l'intérêt d'un système de transport utilisant une combinaison de nanoparticules permettant de contrôler la délivrance dans les ganglions lymphatiques de petites molécules capables d'interagir avec un grand nombre de cellules immunitaires et d'améliorer ainsi l'efficacité d'immunothérapies

Programmable multistage drug delivery to lymph nodes

Schudel, Alex ; Chapman, Asheley Poole ; Yau, Mei-Kwan ; Higginson, Cody James ; Francis, David Mark ; Manspeaker, Margaret Patricia ; Avecilla, Alexa Regina Chua ; Rohner, Nathan Andrew ; Finn, M. G. ; Thomas, Susan Napier

Therapeutic delivery selectively to lymph nodes has the potential to address a variety of unmet clinical needs. However, owing to the unique structure of the lymphatics and the size-restrictive nature of the lymph node reticular network, delivering cargo to specific cells in the lymph node cortex and paracortex is difficult. Here, we describe a delivery system to overcome lymphatic and intra-lymph node transport barriers by combining nanoparticles that are rapidly conveyed to draining lymph [...]

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence un mécanisme par lequel l'ibuprofène, en réduisant l'expression de l'histone désacétylase et de l'histone déméthylase et en supprimant l'expression de certains gènes via une voie dépendante de la cyclo-oxygénase COX2, modifie les propriétés des cellules souches cancéreuses

Ibuprofen mediates histone modification to diminish cancer cell stemness properties via a COX2-dependent manner

Shen, Wenzhi ; Zhang, Xiaoyuan ; Du, Renle ; Gao, Wenjuan ; Wang, Juan ; Bao, Yonghua ; Yang, Wancai ; Luo, Na ; Li, Jianjun

Background : The anticancer potential of ibuprofen has created a broad interest to explore the clinical benefits of ibuprofen in cancer therapy. However, the current understanding of the molecular mechanisms involved in the anticancer potential of ibuprofen remains limited. Methods : Cancer stemness assays to validate ibuprofen function in vitro and in vivo. Histone modification assays to check the effect of ibuprofen on histone acetylation/methylation, as well as the activity of HDAC and [...]

Menée à partir de l'analyse du transcriptome de 38 échantillons de tumeurs primitives ou de métastases provenant de 8 patientes atteintes d'un cancer séreux de l'ovaire de haut grade, cette étude met en évidence l'hétérogénéité du micro-environnement immunitaire de la tumeur ainsi que l'effet immunogène de la chimiothérapie

Unraveling tumor–immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy

Jiménez-Sánchez, Alejandro ; Cybulska, Paulina ; Mager, Katherine LaVigne ; Koplev, Simon ; Cast, Oliver ; Couturier, Dominique-Laurent ; Memon, Danish ; Selenica, Pier ; Nikolovski, Ines ; Mazaheri, Yousef ; Bykov, Yonina ; Geyer, Felipe C. ; Macintyre, Geoff ; Gavarró, Lena Morrill ; Drews, Ruben M. ; Gill, Michael B. ; Papanastasiou, Anastasios D. ; Sosa, Ramon E. ; Soslow, Robert A. ; Walther, Tyler ; Shen, Ronglai ; Chi, Dennis S. ; Park, Kay J. ; Hollmann, Travis ; Reis-Filho, Jorge S. ; Markowetz, Florian ; Beltrao, Pedro ; Vargas, Hebert Alberto ; Zamarin, Dmitriy ; Brenton, James D. ; Snyder, Alexandra ; Weigelt, Britta ; Sala, Evis ; Miller, Martin L.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor–immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory [...]

Menée à l'aide de lignées cellulaires et de tissus pancréatiques normaux ou cancéreux, cette étude met en évidence l'intérêt de cibler la sortiline, une protéine membranaire, pour inhiber le processus invasif des cellules cancéreuses

The membrane protein sortilin can be targeted to inhibit pancreatic cancer cell invasion

Gao, Fangfang ; Griffin, Nathan ; Faulkner, Sam ; Li, Xiang ; King, Simon J. ; Jobling, Phillip ; Denham, Jim W. ; Jiang, Chen Chen ; Hondermarck, Hubert

Pancreatic cancer has a dismal prognosis and there is no targeted therapy against this malignancy. The neuronal membrane protein sortilin is emerging as a regulator of cancer cell development, but its expression and impact in pancreatic cancer is unknown. In this study, we found that sortilin expression was higher in pancreatic cell lines vs normal pancreatic ductal epithelial cells, as demonstrated by Western blot and mass spectrometry. The increased sortilin level in pancreatic cancer cells [...]

Menée à partir de l'analyse de 592 tumeurs issues de patients atteints d'un carcinome rénal à cellules claires de stade avancé, cette étude met en en évidence une corrélation entre des altérations somatiques, le type de cellules immunitaires ayant infiltré la tumeur et l'efficacité des inhibiteurs de PD-1

Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma

Braun, David A. ; Hou, Yue ; Bakouny, Ziad ; Ficial, Miriam ; Sant’ Angelo, Miriam ; Forman, Juliet ; Ross-Macdonald, Petra ; Berger, Ashton C. ; Jegede, Opeyemi A. ; Elagina, Liudmilla ; Steinharter, John ; Sun, Maxine ; Wind-Rotolo, Megan ; Pignon, Jean-Christophe ; Cherniack, Andrew D. ; Lichtenstein, Lee ; Neuberg, Donna ; Catalano, Paul ; Freeman, Gordon J. ; Sharpe, Arlene H. ; McDermott, David F. ; Van Allen, Eliezer M. ; Signoretti, Sabina ; Wu, Catherine J. ; Shukla, Sachet A. ; Choueiri, Toni K.

PD-1 blockade has transformed the management of advanced clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of the PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors from patients with advanced ccRCC enrolled in prospective clinical trials of treatment with PD-1 blockade by whole-exome and RNA sequencing, integrated with immunofluorescence analysis, to uncover the immunogenomic determinants of the therapeutic response. Although conventional genomic [...]

Menée in vitro et à l'aide de xénogreffes dérivées de patients, cette étude met en évidence l'intérêt d'une stratégie thérapeutique consistant à cibler l'expression de l'oncoprotéine MDM2 pour inhiber la synthèse de la sérine et supprimer ainsi la croissance d'un liposarcome

Targeting MDM2-dependent serine metabolism as a therapeutic strategy for liposarcoma

Cissé, Madi Y. ; Pyrdziak, Samuel ; Firmin, Nelly ; Gayte, Laurie ; Heuillet, Maud ; Bellvert, Floriant ; Fuentes, Maryse ; Delpech, Hélène ; Riscal, Romain ; Arena, Giuseppe ; Chibon, Frédéric ; Le Gellec, Sophie ; Maran-Gonzalez, Aurélie ; Chateau, Marie-Christine ; Theillet, Charles ; Carrère, Sébastien ; Portais, Jean-Charles ; Le Cam, Laurent ; Linares, Laetitia K.

The oncogene MDM2 is best known for encoding a protein that helps degrade p53, a key tumor suppressor. However, it also has other oncogenic effects, and Cissé et al. have uncovered one that affects serine metabolism in liposarcoma, a type of soft tissue cancer. The authors showed that in this tumor type, MDM2 is recruited to chromatin independent of any interaction of p53. Inhibiting MDM2 impairs serine synthesis and increases the cells’ reliance on exogenous serine, which is often in short [...]

Mené sur 41 patients atteints d’une tumeur de stade avancé, cet essai de phase I évalue la dose maximale tolérée et l’efficacité, du point de vue du taux de réponse, de E7449, un inhibiteur de PARP 1/2 et de tankyrase 1/2

First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor

Ruth Plummer, Divyanshu Dua, Nicola Cresti, Yvette Drew (et al.)

Background : This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor. Methods : E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50–800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in [...]

Mené sur 32 patients atteints d’une tumeur neuroendocrine non pancréatique de stade avancé, cet essai de phase II évalue l’efficacité, du point de vue de la survie sans progression à 16 semaines, et la toxicité du nintédanib

Multicenter phase 2 trial of nintedanib in advanced nonpancreatic neuroendocrine tumors

Renuka V. Iyer, Bhavana Konda, Christos Fountzilas (et al.)

Background : Antiangiogenic-targeting agents have low response rates in patients with nonpancreatic neuroendocrine tumors (NETs). Nintedanib is an oral antiangiogenic agent that has inhibitory effects on the fibroblast growth factor receptor, which is highly expressed in NETs. The authors hypothesized that nintedanib would be active in patients with nonpancreatic NETs. Methods : Patients with advanced, grade 1 or 2, nonpancreatic NETs who were receiving a stable dose of somatostatin analogue [...]

Mené sur 27 patients d’un lymphome primitif du médiastin à cellules B réfractaire ou récidivant, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse globale, et la toxicité du camrélizumab en combinaison avec une chimiothérapie à base de gemcitabine, vinorelbine et doxorubicine liposomale pégylée (durée médiane de suivi : 24,8 mois)

Camrelizumab plus gemcitabine, vinorelbine and pegylated liposomal doxorubicin in relapsed/refractory primary mediastinal B-cell lymphoma: a single-arm, open-label, phase 2 trial

Qian Mei, Wen-ying Zhang, Yang Liu, Qingming Yang, John EJ Rasko (et al.)

Purpose: Patients with relapsed/refractory primary mediastinal B-cell lymphoma (rrPMBCL) represent a particularly challenging population to treat, with few life-saving treatment options in the context of a dismal prognosis. Experimental Design: In this open-label, single-arm, phase 2 study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL. [...]

Menée au Japon à partir de données portant sur 193 patients atteints d’un mélanome acrolentigineux de stade avancé et non résécable, cette étude rétrospective évalue l’efficacité, du point de vue du taux de réponse objective, de la survie globale, et la toxicité des anticorps anti-PD1

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: A multicentre study of 193 Japanese patients

Y.Nakamura, K.Namikawa, K.Yoshino, S.Yoshikawa (et al.)

Background : Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the real-world efficacy of anti-PD-1 antibodies in advanced AM. Patients and methods : We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response [...]

Menée au Japon à partir de données portant sur 228 patients atteints d’un cancer du poumon à petites cellules récidivant (âge médian : 78 ans), cette étude analyse les facteurs associés à la survie globale et à la survie à 1 an en lien avec une chimiothérapie de seconde ligne

Survival and Prognostic Factors in Elderly Patients Receiving Second-line Chemotherapy for Relapsed Small-Cell Lung Cancer: Results from the Japanese Joint Committee of Lung Cancer Registry

Satoshi Igawa, Katsuhiko Naoki, Yasushi Shintani (et al.)

Objectives : Most patients with small-cell lung cancer (SCLC) experience relapse because of the emergence of drug-resistant tumor cells. Therefore, second-line therapy is subsequently required to prolong their survival. However, it is unclear whether second-line chemotherapy can provide a survival benefit to elderly patients with relapsed SCLC. Therefore, this study aimed to evaluate survival and identify prognostic factors in an elderly population. Materials and methods : Based on a nationwide [...]

A partir d’une revue de la littérature, cette étude fait le point sur l’efficacité des inhibiteurs de points de contrôle immunitaire pour traiter les patients atteints d’un cancer métastatique de la prostate

Immune-checkpoint inhibitors and metastatic prostate cancer therapy: learning by making mistakes

Claps Mélanie, Mennitto Alessia, Guadalupi Valentina (et al.)

Despite advances in metastatic prostate cancer therapy, expected survival for patients in the castration-resistant phase of disease is poor. Immune-checkpoints inhibitors significantly prolonged life expectancy in some solid tumors and have been evaluated also in advanced stage prostate cancer. The majority of data available derive from preliminary phase I and II trials evaluating CTLA-4 and PD-1 as monotherapy or in combination with each other, vaccines, radiotherapy or targeted/hormonal [...]

Menée à partir de données portant sur 42 patients présentant des métastases péritonéales non résécables ayant pour origine un cancer de l'estomac (âge médian : 51,5 ans), cette étude évalue l'efficacité, du point de vue de la survie globale, et la toxicité d'une chimiothérapie intrapéritonéale pressurisée par aérosols en combinaison avec une chimiothérapie systémique

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer

Alyami, Mohammad ; Bonnot, Pierre-Emmanuel ; Mercier, Frederic ; Laplace, Nathalie ; Villeneuve, Laurent ; Passot, Guillaume ; Bakrin, Naoual ; Kepenekian, Vahan ; Glehen, Olivier

Background : PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC. Methods : A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 [...]

Mené sur 57 patients présentant des métastases hépatiques non résécables ayant pour origine un cancer colorectal (durée médiane de suivi : 38,3 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective et du taux de chirurgie secondaire R0, et la toxicité d'un traitement combinant une chimiothérapie de type mFOLFOX6 et une chimioembolisation intra-artérielle utilisant des perles à élution médicamenteuse chargées en irinotécan

Intra-arterial hepatic beads loaded with irinotecan (DEBIRI) with mFOLFOX6 in unresectable liver metastases from colorectal cancer: a Phase 2 study

Pernot, Simon ; Pellerin, Olivier ; Artru, Pascal ; Montérymard, Carole ; Smith, Denis ; Raoul, Jean-Luc ; de la Fouchardière, Christelle ; Dahan, Laetitia ; Guimbaud, Rosine ; Sefrioui, David ; Jouve, Jean-Louis ; Lepage, Come ; Tougeron, David ; Taieb, Julien ; for, Ffcd-Debiri investigators Collaborators

Background : Chemo-embolisation with drug-eluting beads loaded with irinotecan (DEBIRI) increased survival as compared with intravenous irinotecan in chemorefractory patients with liver-dominant metastases from colorectal cancer (LMCRC). First-line DEBIRI with systemic chemotherapy may increase survival and secondary resection. Methods : In the FFCD-1201 single-arm Phase 2 study, patients with untreated, non-resectable LMCRC received DEBIRI plus mFOLFOX6. Four courses of DEBIRI were performed [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence l'intérêt d'une stratégie thérapeutique consistant à combiner agents perturbateurs vasculaires et photothermie avec nanoparticules d'or

Vascular disrupting agent induced aggregation of gold nanoparticles for photothermally enhanced tumor vascular disruption

Hong, Sheng ; Zheng, Di-Wei ; Zhang, Cheng ; Huang, Qian-Xiao ; Cheng, Si-Xue ; Zhang, Xian-Zheng

Although vascular disrupting agents (VDAs) have been extensively implemented in current clinical tumor therapy, the notable adverse events caused by long-term dosing severely limit the therapeutic efficacy. To improve this therapy, we report a strategy for VDA-induced aggregation of gold nanoparticles to further destroy tumor vascular by photothermal effect. This strategy could effectively disrupt tumor vascular and cut off the nutrition supply after just one treatment. In the murine tumor [...]

Menée à partir de données clinicopathologiques portant sur 248 patient atteints d'un adénocarcinome canalaire du pancréas (âge médian : 64 ans), cette étude évalue l'effet d'un traitement néoadjuvant de type FOLFIRINOX en combinaison ou non avec une chimioradiothérapie sur la réponse immunitaire du microenvironnement tumoral

Tumor microenvironment immune response in pancreatic ductal adenocarcinoma patients treated with neoadjuvant therapy

Michelakos, Theodoros ; Cai, Lei ; Villani, Vincenzo ; Sabbatino, Francesco ; Kontos, Filippos ; Fernandez-del Castillo, Carlos ; Yamada, Teppei ; Neyaz, Azfar ; Taylor, Martin S. ; Deshpande, Vikram ; Kurokawa, Tomohiro ; Ting, David T. ; Qadan, Motaz ; Weekes, Collin D. ; Allen, Jill N. ; Clark, Jeffrey W. ; Hong, Theodore S. ; Ryan, David P. ; Wo, Jennifer Y. ; Warshaw, Andrew L. ; Lillemoe, Keith D. ; Ferrone, Soldano ; Ferrone, Cristina R.

Background : Neoadjuvant FOLFIRINOX and chemoradiation have been utilized to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC. Methods : Clinicopathologic variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). [...]

Menée à l'aide d'un modèle murin de cancer du poumon non à petites cellules résistant aux traitements anti-PD1, cette étude met en évidence l'intérêt d'une stratégie thérapeutique consistant à combiner radiothérapie et inhibition du ligand PD-L1 et de la phosphatase SHP-2

SHP-2 and PD-L1 Inhibition Combined with Radiotherapy Enhances Systemic Antitumor Effects in an Anti–PD-1–Resistant Model of Non–Small Cell Lung Cancer

Chen, Dawei ; Barsoumian, Hampartsoum B. ; Yang, Liangpeng ; Younes, Ahmed I. ; Verma, Vivek ; Hu, Yun ; Menon, Hari ; Wasley, Mark ; Masropour, Fatemeh ; Mosaffa, Sara ; Ozgen, Tugce ; Klein, Katherine ; Cortez, Maria Angelica ; Welsh, James W.

Immune checkpoint inhibitors, such as anti–PD-1/PD-L1, have emerged as promising therapies for advanced non–small cell lung cancer (NSCLC). However, approximately 80% of patients do not respond to immunotherapy given alone because of intrinsic or acquired resistance. Radiotherapy (XRT) can overcome PD-1 resistance and improve treatment outcomes, but its efficacy remains suboptimal. The tyrosine phosphatase SHP-2, expressed in some cancers and in immune cells, has been shown to negatively affect [...]

Cet article passe en revue les fonctions physiopathologiques de l'adénosine extracellulaire et les effets de cette dernière sur l'immunité antitumorale, puis identifie des stratégies anticancéreuses potentielles et analyse leurs limites

The adenosine pathway in immuno-oncology

Allard, Bertrand ; Allard, David ; Buisseret, Laurence ; Stagg, John

Cancer immunotherapy based on immune-checkpoint inhibition or adoptive cell therapy has revolutionized cancer care. Nevertheless, a large proportion of patients do not benefit from such treatments. Over the past decade, remarkable progress has been made in the development of ‘next-generation’ therapeutics in immuno-oncology, with inhibitors of extracellular adenosine (eADO) signalling constituting an expanding class of agents. Induced by tissue hypoxia, inflammation, tissue repair and specific [...]

Cet article passe en revue les différentes techniques de diagnostic moléculaire et les différentes classes de thérapies ciblées concernant les cancers avec amplification, mutation, fusion ou surexpression du gène MET

MET-dependent solid tumours — molecular diagnosis and targeted therapy

Guo, Robin ; Luo, Jia ; Chang, Jason ; Rekhtman, Natasha ; Arcila, Maria ; Drilon, Alexander

Attempts to develop MET-targeted therapies have historically focused on MET-expressing cancers, with limited success. Thus, MET expression in the absence of a genomic marker of MET dependence is a poor predictor of benefit from MET-targeted therapy. However, owing to the development of more sensitive methods of detecting genomic alterations, high-level MET amplification and activating MET mutations or fusions are all now known to be drivers of oncogenesis. MET mutations include those affecting [...]

Cet article passe en revue les études concernant les inhibiteurs des voies de réparation des dommages causés à l'ADN dans le traitement des cancers colorectaux

The DNA Damage Response pathway as a land of therapeutic opportunities for colorectal cancer

Mauri, G. ; Arena, S. ; Siena, S. ; Bardelli, A. ; Sartore-Bianchi, A.

Background : Colorectal cancer (CRC) represents a major cause of cancer deaths worldwide. Although significant progress has been made by molecular and immune therapeutic approaches, prognosis of advanced stage disease is still dismal. Alterations in the DNA damage response (DDR) pathways are emerging as novel targets for treatment across different cancer types. However, even though preclinical studies have shown the potential exploitation of DDR alterations in CRC, systematic and comprehensive [...]

Cet article passe en revue les données des essais évaluant des traitements allégés (par rapport aux traitements standard) chez les patients atteints d'un cancer oropharyngé lié au papillomavirus humain puis présente des recommandations pour la mise en place de ce type d'essai

De-Escalation After DE-ESCALATE and RTOG 1016: A Head and Neck Cancer InterGroup Framework for Future De-Escalation Studies

Mehanna, Hisham ; Rischin, Danny ; Wong, Stuart J. ; Gregoire, Vincent ; Ferris, Robert ; Waldron, John ; Le, Quynh-Thu ; Forster, Martin ; Gillison, Maura ; Laskar, Sarbani ; Tahara, Makoto ; Psyrri, Amanda ; Vermorken, Jan ; Porceddu, Sandro

Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) is increasing rapidly. The younger age, significantly improved prognosis, and relative morbidity of the standard-of-care cisplatin and radiotherapy in this population have led to the popularization of the concept of treatment de-escalation. The recent results of the first 3 randomized de-escalation trials, however, have shown a clear detriment in survival when cisplatin is omitted or substituted. In view of these results, the Head [...]