Menée sur des modèles murins et des lapins, cette étude met en évidence l'intérêt d'un hydrogel composé d'alginate et d'ions Mn2+ pour sensibiliser les tumeurs aux micro-ondes et stimuler l'immunité antitumorale

Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment

Zhu, Yujie ; Yang, Zhijuan ; Pan, Zijian ; Hao, Yu ; Wang, Chunjie ; Dong, Ziliang ; Li, Quguang ; Han, Yikai ; Tian, Longlong ; Feng, Liangzhu ; Liu, Zhuang

Microwave ablation (MWA) as a local tumor ablation strategy suffers from posttreatment tumor recurrence. Development of adjuvant biomaterials to potentiate MWA is therefore of practical significance. Here, the high concentration of Ca2+ fixed by alginate as Ca2+-surplus alginate hydrogel shows enhanced heating efficiency and restricted heating zone under microwave exposure. The high concentration of extracellular Ca2+ synergizes with mild hyperthermia to induce immunogenic cell death by [...]

Menée in vitro et à l'aide de xénogreffes sur un modèle murin, cette étude met en évidence un mécanisme par lequel la protéine exosomale ANGPTL4, surexprimée dans un microenvironnement hypoxique, favorise la radiorésistance des cellules cancéreuses en inhibant la ferroptose

Exosomal protein angiopoietin-like 4 mediated radioresistance of lung cancer by inhibiting ferroptosis under hypoxic microenvironment

Zhang, Yuhong ; Liu, Xinglong ; Zeng, Liang ; Zhao, Xinrui ; Chen, Qianping ; Pan, Yan ; Bai, Yang ; Shao, Chunlin ; Zhang, Jianghong

Background : Hypoxia-mediated radioresistance is a major reason for the adverse radiotherapy outcome of non-small cell lung cancer (NSCLC) in clinical, but the underlying molecular mechanisms are still obscure. Methods : Cellular and exosomal ANGPTL4 proteins under different oxygen status were examined. Colony survival, lipid peroxidation and hallmark proteins were employed to determine the correlation between ferroptosis and radioresistance. Gene regulations, western blot and xenograft models [...]

Menée sur des cellules de gliomes de patients et sur des rats, cette étude met en évidence l'intérêt d'un dispositif implantable stimulé par une source externe d'ultrasons et capable de délivrer des champs électriques alternatifs ajustables pour inhiber la croissance de tumeurs cérébrales

An implantable ultrasound-powered device for the treatment of brain cancer using electromagnetic fields

Yang, Yilin ; Hu, Xiaoping ; Liu, Yuxin ; Ouyang, Bin ; Zhang, Jiaxi ; Jin, Huawei ; Yu, Zhenhua ; Liu, Ruiwei ; Li, Zhe ; Jiang, Lelun ; Lin, Xudong ; Xu, Bingzhe

Brain tumors have been proved challenging to treat. Here, we present a promising alternative by developing an implantable ultrasound-powered tumor treating device (UP-TTD) that electromagnetically disrupts the rapid division of cancer cells without any adverse effects on normal neurons, thereby safely inhibiting brain cancer recurrence. In vitro and in vivo experiments confirmed the significant therapeutic effect of the UP-TTD, with ~58% inhibition on growth rate of clinical tumor cells and [...]

Menée à l'aide de lignées cellulaires cancéreuses et de xénogreffes sur des modèles murins, cette étude met en évidence un mécanisme par lequel la protéine MDR1, impliquée dans l'efflux des médicaments, favorise la résistance des cellules cancéreuses aux chimères ciblant la protéolyse, une nouvelle classe thérapeutique

The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells

Kurimchak, Alison M. ; Herrera-Montávez, Carlos ; Montserrat-Sangrà, Sara ; Araiza-Olivera, Daniela ; Hu, Jianping ; Neumann-Domer, Ryan ; Kuruvilla, Mathew ; Bellacosa, Alfonso ; Testa, Joseph R. ; Jin, Jian ; Duncan, James S.

Proteolysis-targeting chimeras (PROTACs) are a promising new class of drugs that selectively degrade cellular proteins of interest. PROTACs that target oncogene products are avidly being explored for cancer therapies, and several are currently in clinical trials. Drug resistance is a substantial challenge in clinical oncology, and resistance to PROTACs has been reported in several cancer cell models. Here, using proteomic analysis, we found intrinsic and acquired resistance mechanisms to [...]

Menée in vitro et in vivo, cette étude met en évidence l'intérêt d'un inhibiteur spécifique de l'activité enzymatique de JMJD6 pour supprimer le développement de plusieurs types de cancer

A specific JMJD6 inhibitor potently suppresses multiple types of cancers both in vitro and in vivo

Xiao, Rong-quan ; Ran, Ting ; Huang, Qi-xuan ; Hu, Guo-sheng ; Fan, Da-meng ; Yi, Jia ; Liu, Wen

Jumonji C-domain-containing protein 6 (JMJD6), an iron (Fe2+) and α-ketoglutarate (α-KG)-dependent oxygenase, is expressed at high levels, correlated with poor prognosis, and considered as a therapeutic target in multiple cancer types. However, specific JMJD6 inhibitors that are potent in suppressing tumorigenesis have not been reported so far. We herein report that iJMJD6, a specific small-molecule inhibitor of JMJD6 with favorable physiochemical properties, inhibits the enzymatic activity of [...]

Menée in vitro et à l'aide d'un modèle murin de mélanome, cette étude met en évidence l'intérêt de nanoparticules cationiques pour améliorer l'efficacité thérapeutique d'un vaccin

Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine

Smith, Rasheid ; Wafa, Emad I. ; Geary, Sean M. ; Ebeid, Kareem ; Alhaj-Suliman, Suhaila O. ; Salem, Aliasger K.

In clinical settings, cancer vaccines as monotherapies have displayed limited success compared to other cancer immunotherapeutic treatments. Nanoscale formulations have the ability to increase the efficacy of cancer vaccines by combatting the immunosuppressive nature of the tumor microenvironment. Here, we have synthesized a previously unexplored cationic polymeric nanoparticle formulation using polyamidoamine dendrimers and poly(d,l-lactic-co-glycolic acid) that demonstrate adjuvant properties [...]

Menée à l'aide de modèles murins, cette étude démontre que les inhibiteurs de point de contrôle immunitaire peuvent réduire la qualité et la quantité des ovocytes

Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice

Winship, Amy L. ; Alesi, Lauren R. ; Sant, Sneha ; Stringer, Jessica M. ; Cantavenera, Aldana ; Hegarty, Teharn ; Requesens, Carolina Lliberos ; Liew, Seng H. ; Sarma, Urooza ; Griffiths, Meaghan J. ; Zerafa, Nadeen ; Fox, Stephen B. ; Brown, Emmaline ; Caramia, Franco ; Zareie, Pirooz ; La Gruta, Nicole L. ; Phillips, Kelly-Anne ; Strasser, Andreas ; Loi, Sherene ; Hutt, Karla J.

Loss of fertility is a major concern for female reproductive-age cancer survivors, since a common side-effect of conventional cytotoxic cancer therapies is permanent damage to the ovary. While immunotherapies are increasingly becoming a standard of care for many cancers—including in the curative setting—their impacts on ovarian function and fertility are unknown. We evaluated the effect of immune checkpoint inhibitors blocking programmed cell death protein ligand 1 and cytotoxic T [...]

Menée à l'aide de lignées cellulaires de cancer du poumon et de xénogreffes sur un modèle murin, cette étude démontre que les fibroblastes associés au cancer peuvent, en fonction du contexte de signalisation, sensibiliser ou non les cellules cancéreuses aux anticancéreux

IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells

Remsing Rix, Lily L. ; Sumi, Natalia J. ; Hu, Qianqian ; Desai, Bina ; Bryant, Annamarie T. ; Li, Xueli ; Welsh, Eric A. ; Fang, Bin ; Kinose, Fumi ; Kuenzi, Brent M. ; Chen, Y. Ann ; Antonia, Scott J. ; Lovly, Christine M. ; Koomen, John M. ; Haura, Eric B. ; Marusyk, Andriy ; Rix, Uwe

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are often linked to drug resistance. Here, we found that coculture with CAFs or culture in CAF-conditioned medium unexpectedly induced drug sensitivity in certain lung cancer cell lines. Gene expression and secretome analyses of CAFs and normal lung?associated fibroblasts (NAFs) revealed differential abundance of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs), which promoted or inhibited, respectively, [...]

Menée in vitro et à l'aide d'un modèle de xénogreffe de glioblastome, cette étude met en évidence l'intérêt d'inhiber le récepteur de type 2 de l'angiotensine II pour supprimer la tumeur

Inhibition of the angiotensin II type 2 receptor AT2R is a novel therapeutic strategy for glioblastoma

Perryman, Richard ; Renziehausen, Alexander ; Shaye, Hamidreza ; Kostagianni, Androniki D. ; Tsiailanis, Antonis D. ; Thorne, Thomas ; Chatziathanasiadou, Maria V. ; Sivolapenko, Gregory B. ; El Mubarak, Mohamed Ahmed ; Han, Gye Won ; Zarzycka, Barbara ; Katritch, Vsevolod ; Lebon, Guillaume ; Lo Nigro, Cristiana ; Lattanzio, Laura ; Morse, Sophie V. ; Choi, James J. ; O’Neill, Kevin ; Kanaki, Zoi ; Klinakis, Apostolos ; Crook, Tim ; Cherezov, Vadim ; Tzakos, Andreas G. ; Syed, Nelofer

Glioblastoma (GBM) is an aggressive malignant primary brain tumor with limited therapeutic options. We show that the angiotensin II (AngII) type 2 receptor (AT2R) is a therapeutic target for GBM and that AngII, endogenously produced in GBM cells, promotes proliferation through AT2R. We repurposed EMA401, an AT2R antagonist originally developed as a peripherally restricted analgesic, for GBM and showed that it inhibits the proliferation of AT2R-expressing GBM spheroids and blocks their [...]

Cet article passe en revue les essais évaluant l'intérêt des immunothérapies à base de lymphocytes CAR-T chez les patients atteints d'un cancer (lymphome, leucémie et myélome multiple) et propose des pistes de développement

Chimeric antigen receptor T cell therapy for cancer: clinical applications and practical considerations

Maakaron, Joseph E ; Hu, Marie ; El Jurdi, Najla

Chimeric antigen receptor T cells have revolutionized the treatment of hematological malignancies during the past five years, boasting impressive response rates and durable remissions for patients who previously had no viable options. In this review, we provide a brief historical overview of their development. We focus on the practical aspects of a patient’s journey through this treatment and the unique toxicities and current best practices to manage those. We then discuss the key registration [...]

Mené dans 9 pays sur 209 patients atteints d'un mélanome de stade métastatique présentant la mutation V600 au niveau du gène BRAF (durée médiane de suivi : 32,2 mois), cet essai de phase II à 3 bras évalue l'efficacité, du point de vue de la survie globale à 2 ans, et la toxicité de trois stratégies thérapeutiques à base d'ipilimumab, de nivolumab, d'encorafénib et de binimétinib dispensés de façon séquentielle

Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial

Paolo A. Ascierto ; Mario Mandala ; Pier Francesso Ferrucci ; Massimo Guidoboni ; Piotr Rutkowski ; Virginia Ferraresi ; Ana Arance ; Michele Guida ; Evaristo Maiello ; Helen Gogas ; Erika Richtig ; Maria Teresa Fierro ; Celeste Lebbé ; Hildur Helgadottir ; Paola Queirolo ; Francesco Spagnolo ; Marco Tucci ; Michele Del Vecchio ; Maria Gonzales Cao ; Alessandro Marco Minisini ; Sabino De Placido ; Miguel F. Sanmamed ; Domenico Mallardo ; Marcello Curvietto ; Ignacio Melero ; Giuseppe Palmieri ; Antonio M. Grimaldi ; Diana Giannarelli ; Reinhard Dummer ; Vanna Chiarion Sileni

PURPOSE : Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for BRAFV600-mutant metastatic melanoma. METHODS : SECOMBIT is a randomized, three-arm, noncom : parative phase II trial (ClinicalTrials.gov identifier: NCT02631447). Patients with untreated, metastatic BRAFV600-mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive [...]

Mené sur 43 patients atteints d'un mélanome muqueux (durée médiane de suivi : 13,4 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement de première ligne combinant atézolizumab et bévacizumab

Atezolizumab Plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: a Multicenter, Open-label, Single-arm Phase 2 Study

Mao, Lili ; Fang, Meiyu ; Chen, Yu ; Wei, Xiaoting ; Cao, Jun ; Lin, Jing ; Zhang, Peng ; Chen, Ling ; Cao, Xiao ; Chen, Yujun ; Guo, Jun ; Si, Lu

Background: Anti-programed cell death-1 monotherapy is part of standard therapy for cutaneous melanoma but has low efficacy in mucosal melanoma. We evaluated the efficacy and safety of atezolizumab plus bevacizumab as first-line therapy for advanced mucosal melanoma. Patients and methods: This multicenter, open-label, single-arm, phase II study utilized a Simon’s two-stage design. Atezolizumab (fixed-dose, 1200 mg) and bevacizumab (7.5 mg/kg) were administered by intravenous infusion every 3 [...]

Mené sur 124 patients atteints d'un myélome multiple réfactaire ou récidivant (âge médian : 68 ans), cet essai de phase I évalue la dose maximale tolérée de ABBV-383, un anticorps bispécifique ciblant l'antigène CD3 exprimé à la surface des lymphocytes T

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma

Anita D'Souza ; Nina Shah ; Cesar Rodriguez ; Peter M. Voorhees ; Katja Weisel, MD ; Orlando F. Bueno ; Rajvineeth K. Pothacamury ; Kevin J. Freise ; Susan Yue ; Jeremy A. Ross ; Akshanth R. Polepally ; Chetasi Talati ; Shane Lee, MS ; Ziyi Jin ; Ben Buelow ; Ravi Vij ; Shaji Kumar

PURPOSE : ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study. METHODS : Patients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 [...]

Mené en France et au Canada sur 493 patients atteints d'un cancer du pancréas ayant été réséqué (âge moyen : 62 ans ; durée médiane de suivi : 69,7 mois), cet essai de phase III compare l'efficacité, du point de vue de la survie sans maladie et de la survie globale à 5 ans, d'un traitement adjuvant de type FOLFORINOX modifié et de la gemcitabine

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial

Conroy, Thierry ; Castan, Florence ; Lopez, Anthony ; Turpin, Anthony ; Ben Abdelghani, Meher ; Wei, Alice C. ; mitry, emmanuel ; Biagi, James J. ; Evesque, Ludovic ; Artru, Pascal ; Lecomte, Thierry ; Assenat, Eric ; Bauguion, Lucile ; Ychou, Marc ; Bouche, Olivier ; Monard, Laure ; Lambert, Aurélien ; Hammel, Pascal ; Canadian Cancer Trials Group ; the Unicancer-GI–PRODIGE Group

Importance : Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available. Objective : To report 5-year outcomes and explore prognostic factors for overall survival. Design, Setting, and Participants : This open-label, phase 3 randomized clinical trial was conducted at 77 [...]

Menée en Israël dans un contexte de vie réelle à partir de données portant sur 102 patients atteints d'un cancer du poumon à petites cellules, cette étude de cohorte rétrospective évalue l'efficacité, du point de vue de la survie globale, des immunothérapies en traitement de première ligne

Real-world evidence for immunotherapy in the first line setting in small cell lung cancer

Sagie, Shira ; Maixner, Nitzan ; Stemmer, Amos ; Lobachov, Anastasiya ; Bar, Jair ; Urban, Damien

Objective : Despite major progress over the past decade in the field of lung cancer care, onlymild advances have occurred in Small Cell Lung Cancer (SCLC), with prognosis remainingpoor. Based on two randomized clinical trials (RCTs), two checkpoint-inhibitors have recently been approved in extensive-SCLC with moderate improvements in median overall survival (OS). However, only limited data exist regarding the impact of immunotherapy in real-world SCLC patients. This study reports the efficacy [...]

Mené sur 102 patients atteints d'un cancer du poumon non à petites cellules EGFR+ de stade IIIA, cet essai de phase II compare l'efficacité, du point de vue de la survie sans maladie et de la survie globale à 5 ans, de l'erlotinib par rapport à une chimiothérapie adjuvante combinant vinorelbine et cisplatine

Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non–Small-Cell Lung Cancer

Dongsheng Yue ; Shidong Xu ; Qun Wang ; Xiaofei Li ; Yi Shen ; Heng Zhao ; Chun Chen ; Weimin Mao ; Wei Liu ; Junfeng Liu ; Lanjun Zhang ; Haitao Ma ; Qiang Li ; Yue Yang ; Yongyu Liu ; Haiquan Chen ; Zhenfa Zhang ; Bin Zhang ; Changli Wang

The randomized, open-label, phase II EVAN study investigated the efficacy (disease-free survival [DFS] and 5-year overall survival [OS]) and safety of erlotinib versus vinorelbine/cisplatin as adjuvant chemotherapy after complete resection (R0) for stage III epidermal growth factor receptor (EGFR) mutation+ non–small-cell lung cancer. We describe the updated results at the 43-month follow-up. In EVAN, patients were randomly assigned (1:1) to erlotinib (n = 51) or vinorelbine/cisplatin (n = 51). [...]

Cette étude passe en revue les données évaluant l'efficacité du régorafénib en combinaison avec des inhibiteurs de point de contrôle immunitaire chez des patients atteints d'un cancer colorectal avec microsatellites stables et ne présentant pas de déficience MMR

Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer

Akin Telli, Tugba ; Bregni, Giacomo ; Van Hooren, Michele ; Saude Conde, Rita ; Hendlisz, Alain ; Sclafani, Francesco

Immune checkpoint inhibitors (ICIs) have marked a new era of cancer treatment, showing remarkable efficacy in a wide range of solid malignancies. In colorectal cancer (CRC),however, the therapeutic potential of ICIs is limited to the small group (≈5%) of patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H)tumours, which are characterised by high mutational/neo-antigen burden, and an inflammatorytumour microenvironment with abundant tumour-infiltrating lymphocytes. [...]

Mené sur 543 patientes atteintes d'un cancer du sein HR+ HER2- de stade métastatique (âge médian : 56 ans), cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du sacituzumab govitécan, un conjugué anticorps-médicament ciblant la protéine Trop-2

Sacituzumab Govitecan in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

Hope S. Rugo ; Aditya Bardia ; Frederik Marmé ; Javier Cortes ; Peter Schmid ; Delphine Loirat ; Olivier Trédan ; Eva Ciruelos ; Florence Dalenc ; Patricia Gómez Pardo ; Komal L. Jhaveri ; Rosemary Delaney ; Olivia Fu ; Lanjia Lin ; Wendy Verret ; Sara M. Tolaney ; on behalf of the TROPiCS-02 Study Investigators

PURPOSE : Hormone receptor–positive (HR+) human epidermal growth factor receptor 2–negative (HER2–) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer. METHODS : In this global, randomized, phase III study, SG was compared with physician's [...]

Mené sur 20 patientes atteintes d'un cancer du col de l'utérus localement avancé, cet essai de phase II évalue l'efficacité, du point de vue de la réduction de l'hypoxie tumorale, de l'ajout de metformine à une chimioradiothérapie

A Phase II Randomized Trial of Chemoradiation with or without Metformin in Locally Advanced Cervical Cancer

Han, Kathy ; Fyles, Anthony ; Shek, Tina ; Croke, Jennifer ; Dhani, Neesha ; D'Souza, David ; Lee, Ting-Yim ; Chaudary, Naz ; Bruce, Jeff ; Pintilie, Melania ; Cairns, Rob ; Vines, Douglass ; Pakbaz, Sara ; Jaffray, David ; Metser, Ur ; Rouzbahman, Marjan ; Milosevic, Michael ; Koritzinsky, Marianne

Purpose: Tumor hypoxia is associated with poor response to radiation (RT). We previously discovered a novel mechanism of metformin: enhancing tumor RT response by decreasing tumor hypoxia. We hypothesized that metformin would decrease tumor hypoxia and improve cervical cancer response to RT. Experimental Design: A window-of-opportunity, phase II randomized trial was performed in stage IB-IVA cervical cancer. Patients underwent screening positron emission tomography (PET) imaging with hypoxia [...]

Menée auprès de 15 patients atteints d'un cancer des voies biliaires périhilaires ayant subi une résection curative, cette étude analyse l'efficacité d'un traitement séquentiel associant une embolisation de la veine porte et une chimiothérapie avant la chirurgie

Sequential therapy of portal vein embolization and systemic chemotherapy for locally advanced perihilar biliary tract cancer

Takahashi, Atsushi ; Yoshioka, Ryuji ; Miyashita, Mamiko ; Tanaka, Haruka ; Oba, Masaru ; Ichida, Hirofumi ; Imamura, Hiroshi ; Mise, Yoshihiro ; Saiura, Akio

Background: Curative resection is the only potential treatment for cure in patients with perihilar biliary tract cancer (PBTC). However, post hepatectomy liver failure (PHLF) due to insufficient future liver remnant volume (FRLV) remains a lingering risk even after portal vein embolization (PVE). This study aimed to investigate the feasibility and efficacy of a sequential treatment strategy consisting of PVE followed by preoperative chemotherapy before surgery. Methods: Between April 2019 and [...]

Cet article passe en revue les connaissances concernant les traitements anticancéreux ciblant RAS

The current state of the art and future trends in RAS-targeted cancer therapies

Punekar, Salman R. ; Velcheti, Vamsidhar ; Neel, Benjamin G. ; Wong, Kwok-Kin

Despite being the most frequently altered oncogenic protein in solid tumours, KRAS has historically been considered ‘undruggable’ owing to a lack of pharmacologically targetable pockets within the mutant isoforms. However, improvements in drug design have culminated in the development of inhibitors that are selective for mutant KRAS in its active or inactive state. Some of these inhibitors have proven efficacy in patients with KRASG12C-mutant cancers and have become practice changing. The [...]

Menée à partir notamment d'échantillons plasmatiques et d'échantillons tissulaires de métastases synchrones provenant de patients atteints d'un cancer métastatique de la prostate résistant à la castration, cette étude met en évidence l'intérêt de l'ADN tumoral circulant pour étudier la progression des cancers métastatiques, notamment l'acquisition d'une résistance thérapeutique

Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer

Herberts, Cameron ; Annala, Matti ; Sipola, Joonatan ; Ng, Sarah W. S. ; Chen, Xinyi E. ; Nurminen, Anssi ; Korhonen, Olga V. ; Munzur, Aslı D. ; Beja, Kevin ; Schönlau, Elena ; Bernales, Cecily Q. ; Ritch, Elie ; Bacon, Jack V. W. ; Lack, Nathan A. ; Nykter, Matti ; Aggarwal, Rahul ; Small, Eric J. ; Gleave, Martin E. ; Quigley, David A. ; Feng, Felix Y. ; Chi, Kim N. ; Wyatt, Alexander W. ; Su C. Pcf West Coast Prostate Cancer Dream Team

Circulating tumour DNA (ctDNA) in blood plasma is an emerging tool for clinical cancer genotyping and longitudinal disease monitoring1. However, owing to past emphasis on targeted and low-resolution profiling approaches, our understanding of the distinct populations that comprise bulk ctDNA is incomplete2–12. Here we perform deep whole-genome sequencing of serial plasma and synchronous metastases in patients with aggressive prostate cancer. We comprehensively assess all classes of genomic [...]