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JOURNAL ARTICLE
Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B Villafania, Jennifer L Sauter, Michael Offin, Marjorie G Zauderer, Marc Ladanyi
PURPOSE: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined. EXPERIMENTAL DESIGN: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using the FACETS algorithm. RESULTS: 210 patients were evaluable for LOH analysis using FACETS...
April 17, 2024: Clinical Cancer Research
#2
JOURNAL ARTICLE
Jon Zugazagoitia, Handerson Osma, Javier Baena, Álvaro C Ucero, Luis Paz-Ares
Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be prominently altered in human SCLC, including, among others, T cell exclusion, downregulation of components of the MHC-class I antigen processing and presentation machinery, or upregulation of macrophage inhibitory checkpoints...
April 17, 2024: Clinical Cancer Research
#3
JOURNAL ARTICLE
Neeltje Steeghs, Carlos Gomez-Roca, Kristoffer S Rohrberg, Morten Mau-Sørensen, Debbie Robbrecht, Josep Tabernero, Samreen Ahmed, Maria E Rodriguez-Ruiz, Caroline Ardeshir, Daniela Schmid, Nassim Sleiman, Carl Watson, Hanna Piper-Lepoutre, David Dejardin, Stefan Evers, Christophe Boetsch, Jehad Charo, Volker Teichgräber, Ignacio Melero
PURPOSE: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors. METHODS: Participants received FAP-IL2v intravenously once weekly...
April 17, 2024: Clinical Cancer Research
#4
JOURNAL ARTICLE
Melina Peressini, Rosario Garcia-Campelo, Bartomeu Massuti, Cristina Marti, Manuel Cobo, Vanesa Gutiérrez, Manuel Dómine, Jose Fuentes, Margarita Majem, Javier de Castro, Juan Felipe Cordoba, Maria Pilar Diz, Dolores Isla, Emilio Esteban, Enric Carcereny, Laia Vila, Alberto Moreno-Vega, Silverio Ros, Amaia Moreno, Francisco Javier Garcia, Gerardo Huidobro, Carlos Aguado, Victor Cebey-Lopez, Javier Valdivia, Ramon Palmero, Pilar Lianes, Marta Lopez-Brea, Oscar Juan Vidal, Mariano Provencio, Edurne Arriola, Javier Baena, Mercedes Herrera, Helena Bote, Magdalena Molero, Vera Adradas, Santiago Ponce-Aix, Angel Nuñez-Buiza, Álvaro Ucero, Susana Hernandez, Fernando Lopez-Rios, Esther Conde, Luis Paz-Ares, Jon Zugazagoitia
BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial...
April 17, 2024: Clinical Cancer Research
#5
JOURNAL ARTICLE
Alvaro Teijeira, Saray Garasa, Maria C Ochoa, Sandra Sanchez-Gregorio, Gabriel Gomis, Carlos Luri-Rey, Rafael Martinez-Monge, Beatrice Pinci, Karmele Valencia, Belen Palencia, Benigno Barbes, Elixabet Bolanos, Arantza Azpilikueta, Marina Garcia-Cardosa, Javier Burguete, Iñaki Eguren-Santamaria, Eneko Garate-Soraluze, Pedro Berraondo, Jose L Perez-Gracia, Carlos E de Andrea, Maria E Rodriguez-Ruiz, Ignacio Melero
PURPOSE: Cancer patients frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NETs), we have investigated the mechanisms, consequences and the occurrence of such phenomena in patients undergoing radiotherapy. EXPERIMENTAL DESIGN: NETosis was analyzed in cultures of neutrophils isolated from healthy donors, cancer patients and cancer-bearing mice under confocal microscopy...
April 17, 2024: Clinical Cancer Research
#6
JOURNAL ARTICLE
Ursula Grazini, Aleksandra Markovets, Lucy Ireland, Daniel O'Neill, Benjamin Phillips, Man Xu, Matthias Pfeifer, Tereza Vaclova, Matthew J Martin, Ludovic Bigot, Luc Friboulet, Ryan Hartmaier, Maria Emanuela Cuomo, Simon T Barry, Paul D Smith, Nicolas Floc'h
PURPOSE: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for the treatment of EGFR mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line treated patients with EGFRm advanced NSCLC. Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease progression. EXPERIMENTAL DESIGN: ctDNA profiling analysis on-progression plasma samples from patients treated with osimertinib in both first (Phase 3, FLAURA trial) and second-line trials (Phase 3, AURA3 trial) revealed a high prevalence of PIK3CA/AKT/PTEN alterations...
April 17, 2024: Clinical Cancer Research
#7
JOURNAL ARTICLE
Thomas Graillon, Pauline Romanet, Clara Camilla, Camille Gelin, Romain Appay, Catherine Roche, Arnaud Lagarde, Grégory Mougel, Kaissar Farah, Maëlle Le Bras, Julien Engelhardt, Michel Kalamarides, Matthieu Peyre, Aymeric Amelot, Evelyne Emery, Elsa Magro, Helene Cebula, Rabih Aboukais, Catherine Bauters, Emmanuel Jouanneau, Moncef Berhouma, Thomas Cuny, Henry Dufour, Hugues Loiseau, Dominique Figarella-Branger, Luc Bauchet, Christine Binquet, Anne Barlier, Pierre Goudet
PURPOSE: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). EXPERIMENTAL DESIGN: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed-up in the French MEN1 national cohort. Standardized incidence rate (SIR) was calculated based on the French Gironde CNS tumors registry...
April 17, 2024: Clinical Cancer Research
#8
JOURNAL ARTICLE
Birgit S Geurts, Laurien J Zeverijn, Lindsay V M Leek, Jade M van Berge Henegouwen, Louisa R Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Joris van de Haar, Annemiek van Ommen-Nijhof, Marleen Kok, Paul Roepman, Anne M L Jansen, Wendy W J de Leng, Maja J A de Jonge, Ann Hoeben, Carla M L van Herpen, Hans M Westgeest, Lodewyk F A Wessels, Henk M W Verheul, Hans Gelderblom, Emile E Voest
PURPOSE: To evaluate efficacy of pembrolizumab across multiple cancer types harboring different levels of Whole-Genome Sequencing (WGS)-based tumor mutational load (TML; total of non-synonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234). PATIENTS AND METHODS: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in cohort A: breast cancer TML 140-290, cohort B: tumor-agnostic cohort TML 140-290, and cohort C: tumor-agnostic cohort TML >290...
April 17, 2024: Clinical Cancer Research
#9
JOURNAL ARTICLE
Shifeng Lian, Chenyu Lu, Fugui Li, Xia Yu, Limei Ai, Biao-Hua Wu, Xueyi Gong, Wenjing Zhou, Xuejun Liang, Jiyun Zhan, Yong Yuan, Fang Fang, Zhiwei Liu, Mingfang Ji, Zongli Zheng
PURPOSE: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. METHODS: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples)...
April 17, 2024: Clinical Cancer Research
#10
JOURNAL ARTICLE
Toshiaki Iwase, Evan N Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel Layman, David Ramirez, Debu Tripathy, Stacy L Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M Reuben, Naoto T Ueno
PURPOSE: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study. PATIENTS AND METHODS: Patients with a complete response (CR), partial response (PR), or stable disease (SD) after at least 3 cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression...
April 17, 2024: Clinical Cancer Research
#11
JOURNAL ARTICLE
Guangrong Qin, Jin Dai, Sylvia Chien, Timothy J Martins, Brenda Loera, Quy H Nguyen, Melanie L Oakes, Bahar Tercan, Boris Aguilar, Lauren Hagen, Jeannine McCune, Richard Gelinas, Raymond J Monnat, Ilya Shmulevich, Pamela S Becker
PURPOSE: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. EXPERIMENTAL DESIGN: We performed targeted sequencing, high-throughput drug screening, and single-cell genomic profiling on leukemia cell samples derived from patients with AML...
April 15, 2024: Clinical Cancer Research
#12
JOURNAL ARTICLE
Asli Küçükosmanoglu, Silvia Scoarta, Megan Houweling, Nicoleta Spinu, Thomas Wijnands, Niek Geerdink, Carolien Meskers, Georgi K Kanev, Bert Kiewiet, Mathilde Kouwenhoven, David Noske, Tom Wurdinger, Marianne Pouwer, Mark Wolff, Bart A Westerman
PURPOSE: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. EXPERIMENTAL DESIGN: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects...
April 10, 2024: Clinical Cancer Research
#13
JOURNAL ARTICLE
Hyung-Joo Oh, Suk-Chul Bae, In-Jae Oh, Cheol-Kyu Park, Kyoung-Mi Jung, Da-Mi Kim, Jung-Won Lee, Chang Kyun Kang, Il Yeong Park, Young-Chul Kim
PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth...
April 9, 2024: Clinical Cancer Research
#14
JOURNAL ARTICLE
Lena Fischer-Riepe, Sareetha Kailayangiri, Katharina Zimmermann, Rita Pfeifer, Michael Aigner, Bianca Altvater, Sascha Kretschmann, Simon Völkl, Jordan Hartley, Celine Dreger, Katja Petry, Andreas Bosio, Angelika von Döllen, Wolfgang Hartmann, Holger Lode, Dennis Görlich, Andreas Mackensen, Melanie Jungblut, Axel Schambach, Hinrich Abken, Claudia Rossig
PURPOSE: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers. EXPERIMENTAL DESIGN: We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response and cytolytic effector functions in the tumor microenvironment...
April 9, 2024: Clinical Cancer Research
#15
JOURNAL ARTICLE
Sophie Archer, Phillip M Brailey, Minjung Song, Phillip D Bartlett, Ines Figueiredo, Bora Gurel, Christina Guo, Verena Brucklacher-Waldert, H Lorraine Thompson, Jude Akinwale, Samantha E Boyle, Christine Rossant, Neil R Birkett, Julia Pizzey, Mark Maginn, James Legg, Richard Williams, Colette M Johnston, Philip Bland-Ward, Johann S de Bono, Andrew J Pierce
PURPOSE: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. A CD137 agonist targeted to the prostate-specific membrane antigen (PSMA), frequently and highly expressed on castration-resistant metastatic prostate cancer (mCRPC) tumor cells, could bring effective immunotherapy to this immunologically challenging to address disease...
April 9, 2024: Clinical Cancer Research
#16
JOURNAL ARTICLE
Christoph A Schatz, Sabine Zitzmann-Kolbe, Ingrid Moen, Monika Klotz, Shankari Nair, Stefan Stargard, Roger M Bjerke, Katrine Wickstrøm Biseth, Yuan Zeng Feng, Bård Indrevoll, Véronique Cruciani, Jenny Karlsson, Bernard Haendler, Carsten H Nielsen, Maria Z Alfsen, Stefanie Hammer, Hartwig Hennekes, Alan Cuthbertson, Urs B Hagemann, Aasmund Larsen
PURPOSE: Initially, prostate cancer responds to hormone therapy but eventually resistance develops. Beta emitter-based PSMA (prostate-specific membrane antigen)-targeted radionuclide therapy is approved for the treatment of metastatic castration-resistant prostate cancer. Here we introduce a targeted alpha therapy (TAT) consisting of the PSMA antibody pelgifatamab covalently linked to a macropa chelator and labeled with actinium-225 and compare its efficacy and tolerability with other TATs...
April 9, 2024: Clinical Cancer Research
#17
JOURNAL ARTICLE
Sangini S Sheth, Ji Eun Oh, Stefania Bellone, Eric R Siegel, Michelle Greenman, Levent Mutlu, Blair McNamara, Shefali Pathy, Mitchell Clark, Masoud Azodi, Gary Altwerger, Vaagn Andikyan, Gloria Huang, Elena Ratner, Daniel J Kim, Akiko Iwasaki, Angelique W Levi, Natalia Buza, Pei Hui, Sean Flaherty, Peter E Schwartz, Alessandro D Santin
PURPOSE: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. PATIENTS AND METHODS: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A)...
April 9, 2024: Clinical Cancer Research
#18
JOURNAL ARTICLE
Farah Ballout, Heng Lu, Nadeem Bhat, Lei Chen, Dunfa Peng, Zheng Chen, Steven Chen, Xiaodian Sun, Silvia Giordano, Simona Corso, Alexander Zaika, Oliver McDonald, Alan S Livingstone, Wael El-Rifai
PURPOSE: TGFβ signaling is implicated in the progression of most cancers, including esophageal adenocarcinoma (EAC). Emerging evidence indicates that TGFβ signaling is a key factor in the development of resistance toward cancer therapy. EXPERIMENTAL DESIGN: In this study, we developed patient-derived organoids and patient-derived xenograft models of EAC and performed bioinformatics analysis combined with functional genetics to investigate the role of SMAD family member 3 (SMAD3) in EAC resistance to oxaliplatin...
April 9, 2024: Clinical Cancer Research
#19
JOURNAL ARTICLE
Hyungseok Cho, Seok-Soo Byun, Nak-Hoon Son, Jae Il Chung, Won Ik Seo, Chan Ho Lee, Todd M Morgan, Ki-Ho Han, Jae-Seung Chung
PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]...
April 8, 2024: Clinical Cancer Research
#20
JOURNAL ARTICLE
Lanlan Pang, Yihua Huang, Weitao Zhuang, Yaxiong Zhang, Jun Liao, Yue Hao, Feng Hao, Guoqian Wang, Ze-Xin Chase Chen, Yu Zhu, Mengzhen Li, Zhengbo Song, Bo Peng Deng, Jing Li, Li Zhang, Wenfeng Fang
PURPOSE: Current NCCN guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4228 treatment-naïve patients with lung cancer who underwent targeted NGS testing was screened for EGFR p...
April 5, 2024: Clinical Cancer Research
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